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Post cesarean analgesia
Post Cesarean Analgesia Craig M. Palmer, MD
There are a variety of effective options for postcesarean analgesia. A single epidural injection of 4 mg of morphine provides 18 to 24 hours of good to excellent analgesia. A single spinal injection of 0.1 mg of morphine also provides 18 to 24 hours of analgesia. Continuous epidural catheter techniques can be effective, usually by relying on a combination of a short-acting opioid, such as fentanyl or sufentanil, and a local anesthetic, usually bupivacaine or ropivacaine. Occasionally, with this technique, motor block caused by the local anesthetic interferes with maternal ambulation. Patient-controlled techniques, either intravenous or epidural, also have proven effective. A variety of opioids (including morphine, meperidine, and fentanyl) have been used for intravenous patient-controlled analgesia with little to recommend one drug over the other. For epidural patientcontrolled analgesia, opioid–local anesthetic combinations are usually used, with delivery parameters dependent on the exact concentration of the chosen solution. Regardless of the technique chosen, careful monitoring of patients in the early postoperative period (24 hours) is essential to avoid adverse effects and to ensure maternal satisfaction. © 2003 Elsevier Inc. All rights reserved.
esarean delivery is the most frequently performed inpatient operation in the United States and probably throughout the world. In the last two decades, our improved understanding of central nervous system pharmacology and improvements in technology have changed the way we provide postoperative analgesia in both obstetric and surgical patients. For many years, intramuscular narcotics were the mainstay of analgesia after cesarean delivery; in some settings, they still are. Today, considering our knowledge of and experience with postoperative pain management in this population, planning an anesthetic for cesarean delivery also should include planning for adequate postoperative analgesia.
C
Epidural Morphine Though the idea that cell-membrane receptors can mediate drug effects was first postulated in the 1800’s, only in the last few decades has substantial progress been made in the area of receptor pharmacology. By the mid-1970’s, two subtypes of opioid receptors, mu and kappa, had been described and characterized.1 A third opioid-receptor subtype, the delta receptor, was described shortly thereafter.2 In 1975, enkephalins, a form of endogenous opioid, were isolated and characterized. By the From the Department of Anesthesiology, University of Arizona Health Sciences Center, Tucson, AZ. Address reprint requests to: Craig M. Palmer, MD, Department of Anesthesiology, University of Arizona Health Sciences Center, P.O. Box 245114, Tucson, AZ 85724. © 2003 Elsevier Inc. All rights reserved. 1084-208X/03/0704-0007$30.00/0 doi:10.1016/S1084-208X(03)00039-9
late 1970’s, autoradiographic mapping had revealed opioidreceptor distribution within the central nervous system. High concentrations of opioid receptors are found in the substantia gelatinosa of the spinal cord, the medullary dorsal horn, and periaquaductal gray matter of the midbrain (Fig 1). In 1977, intrathecal morphine was demonstrated to produce high-quality, naloxone-reversible analgesia in the rat.3 By 1979, epidural morphine was reported to be an effective analgesic in cancer patients.4 Shortly thereafter, a number of series reported epidural morphine provided effective postcesarean analgesia in doses ranging from 2 to 10 mg.5-8 Morphine is the most widely used epidural opioid for analgesia after cesarean section. Pain relief from epidural morphine for postcesarean analgesia follows a consistent dose-response relationship.9 As the dose of epidural morphine increases, analgesia improves until the dose reaches about 4 mg (Figs 2 and 3). This dose provides 18 to 24 hours of good to excellent analgesia. Increasing the dose above 4 mg does not further improve analgesia, but does increase the frequency and severity of adverse effects. Volume of diluent is not a major factor in epidural morphine analgesia; a volume of 5 to 10 mL is generally adequate.10 Because of interindividual differences, some patients will require additional analgesics (see below). A higher failure rate (ie, diminished analgesia) becomes apparent when using less than 3 mg of epidural morphine.
Adverse Effects of Epidural Morphine Pruritus Although an effective analgesic, epidural morphine does have significant adverse effects, with pruritus being the most common. Pruritus characteristically occurs on the face or trunk, although it may be generalized. In the clinically used range, pruritus is not significantly dose-related (Fig 4).9 The exact mechanism by which epidural morphine causes pruritus is unknown.11,12 The available evidence indicates it to be more complex than a simple receptor-related issue. The role of opioid receptors in pruritus may primarily be via facilitation of other excitatory neuronal pathways and protective reflexes. A full understanding of the phenomenon awaits further investigation.
Nausea and Vomiting Nausea and vomiting are infrequent after epidural morphine. In some series, the reported incidence ranges from 11% to about 30%,6,13 but others have found the incidence to be no different than placebo.9 Epidural morphine can cause nausea and vomiting by stimulating the chemoreceptor trigger zone located in the base of the fourth ventricle of the brain. Morphine, which is highly hydrophilic, remains free (unbound) in the cerebrospinal fluid for a significantly longer time than more lipophilic opioids (ie, fentanyl or sufentanil). Morphine concentration in cervical cerebrospinal fluid peaks 3 to 4 hours after injection.14
Techniques in Regional Anesthesia and Pain Management, Vol 7, No 4 (October), 2003: pp 213-221
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Fig 1. The dorsal horn of the lumbar spinal cord. Afferent sensation is carried primarily by Type C and A neurons, which synapse primarily in Lamina II, the substantia gelatinosa. Opioid receptors (the small squares in the cell membranes) are located presynaptically on type C fibers, but not type A fibers; they are also located postsynaptically on interneurons and projection neurons. About 75% of opioid receptors are located presynaptically, with ⬃25% postsynaptically.
Radiographic studies of other water-soluble compounds confirm that cephalad migration in the cerebrospinal fluid does occur.15
Respiratory Depression Shortly after its introduction to clinical use, respiratory depression was recognized as a complication of epidural morphine. The risk at clinically used doses is quite low, however. A retrospective review of 4,880 parturients receiving epidural morphine after cesarean delivery found a respiratory rate below 10 in only 12 patients, or 0.25%.13 A prospective study of 1,000
Fig 2. Twenty-four-hour PCA morphine use after varying doses of epidural morphine. Data are mean (ⴞSEM) Reprinted with permission from Palmer CM, D’Angelo R, Paech MJ: Handbook of Obstetric Anesthesia. Oxford: Bios Scientific Publishers, 2002. Adapted from Palmer CM, Nogami WM, Van Maren G, et al: Postcesarean epidural morphine: a dose response study. Anesth Analg 90:887-891, 2000.
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Fig 3. Cumulative PCA morphine use after varying doses of epidural morphine. Data are mean (ⴞSEM), and are slightly offset for clarity. Reprinted with permission from Palmer CM, D’Angelo R, Paech MJ: Handbook of Obstetric Anesthesia. Oxford: Bios Scientific Publishers, 2002. Adapted from Palmer CM, Nogami WM, Van Maren G, et al: Postcesarean epidural morphine: a dose response study. Anesth Analg 90:887-891, 2000.
parturients who received morphine, 5 mg epidurally, reported 4 patients with a respiratory rate of below 10 (0.4%).16 The incidence of clinically significant respiratory depression after epidural morphine at doses of 5 mg or less in the obstetric population is at most 0.2% to 0.3%. Respiratory depression after epidural morphine is usually described as “late,” with an onset between 6 and 12 hours after administration. This “delayed” depression is caused by the slow cephalad migration of epidurally administered morphine, which can cause direct central depression of respiration. Untreated, a gradual decline in respiratory rate leads to progressive respiratory acidosis. Based on case reports, the risk of respiratory depression probably rises as the dose increases, at least
Fig 4. Cumulative 24-hour pruritus scores after varying doses of epidural morphine. Data are mean (standard error). *Itching in the control group (group 0) was significantly lower than the 4 epidural morphine groups, which were not different from each other. Reprinted with permission from Palmer CM, D’Angelo R, Paech MJ: Handbook of Obstetric Anesthesia. Oxford: Bios Scientific Publishers, 2002. Adapted from Palmer CM, Nogami WM, Van Maren G, et al: Postcesarean epidural morphine: a dose response study. Anesth Analg 90:887-891, 2000. CRAIG M. PALMER
TABLE 1. Side Effects of Neuraxial Morphine Side Effect
Incidence
Treatment
Comments
Pruritus
Up to 90-100%
Usually mild; Naloxone rarely necessary
Nausea and vomiting
Probably ⬍10%
Respiratory depression
⬍0.25%
Nalbuphine 5 mg IV Or diphenhydramine 12.5-25 mg IV Or naloxone 0.04-0.2 mg IV Ondansetron 4 mg IV or droperidol 0.625 mg IV Naloxone 0.2-0.4 mg IV. Assisted ventilation if necessary
beyond 5 mg. Other factors such as obesity and the concomitant administration of other narcotics also increase the risk. Early respiratory depression after epidural morphine also is possible. This event probably arises from rapid systematic uptake or intravascular injection of the drug.
Herpes Simplex Labialis In 1987, Gieraerts et al17 reported the results of a prospective, nonrandomized study of 44 parturients after cesarean delivery. Twenty-six of these patients received epidural morphine at surgery, and up to twice daily thereafter. Another 18 women received intramuscular morphine. Recurrent herpes simplex labialis lesions appeared in 9 of the 26 patients in the epidural group but in none of the patients in the intramuscular group. A later retrospective study15 corroborated their report, finding herpes simplex labialis lesions recurred in 9.7% of patients who received epidural morphine but in only 0.6% of those who did not. Other investigators have been unable to verify this association. Norris et al19 found no differences in the incidence of recurrent herpes simplex labialis among 203 parturients receiving various anesthetics for cesarean section, with or without neuraxial morphine. These disparate findings may represent differences in the study populations, which have not yet been characterized, or other unrecognized factors.
Treatment of Adverse Effects (Table 1) Nalbuphine (5 mg intravenously [IV]) is an effective treatment for pruritus, does not reverse analgesia, and has no significant adverse effects.20,21 It is an excellent first-line choice should treatment be necessary. Diphenhydramine, 12.5 to 25 mg IV, also usually provides adequate symptomatic relief, but the associated sedation may be as instrumental in providing relief as its antihistaminergic effect. In rare cases, naloxone may be necessary to relieve severe pruritus (0.04-0.2 mg IV, followed by a continuous infusion; start at 0.4 to 0.6 mg/h and titrate as needed). Other treatments, including propofol, droperidol, and ondansetron have been reported effective in treating pruritus, but are generally either too costly for routine use or have significant adverse effects themselves.22-24 Treatment options for nausea and vomiting include antiemetics and opioid antagonists. As noted above, nausea and vomiting in this setting are usually not caused by the epidural morphine, and conventional antiemetics should be the first option. Four mg of IV ondansetron or 0.625 mg of droperidol are generally effective treatments. IV nalbuphine at 5 to 10 mg or very low-dose naloxone can relieve nausea and vomiting if it is secondary to epidural morphine. Early or late, the treatment of choice for respiratory depresPOSTCESAREAN ANALGESIA
Usually not related to epidural morphine Very rare in healthy parturients
sion is IV naloxone. Institute artificial or mechanical support of ventilation immediately if the patient is obtunded while waiting for naloxone to take effect. Preemptive therapy to prevent the adverse effects of epidural morphine has been largely disappointing. Although a number of treatments can prevent adverse effects, they generally also either decrease analgesia or cause adverse effects of their own. IV naloxone and oral naltrexone25,26 can prevent adverse effects, but both decrease analgesia in a dose-dependent fashion. Epidural butorphanol modestly decreases adverse effects, but causes somnolence.27 Prophylactic transdermal scopolamine decreases the incidence of nausea and vomiting during the first 24 hours after cesarean delivery, but it must be applied several hours in advance and it causes dry mouth.28 For these reasons, prophylactic treatment is rarely recommended.
Other Epidural Opioids (Table 2) Fentanyl Epidural fentanyl, 50 to 100 g, rapidly provides profound analgesia for up to 4 hours (Fig 5).29 Higher doses neither improve nor prolong pain relief. Epidural fentanyl causes the same adverse effects as morphine, although onset is faster and duration is shorter. Intraoperatively, epidural fentanyl improves patient comfort and may decrease the incidence of nausea and vomiting. Although useful intraoperatively during epidural anesthesia for cesarean delivery, the duration of epidural fentanyl limits its utility as a postoperative analgesic.
Sufentanil The only advantage of epidural sufentanil over epidural morphine is its rapid onset. The incidence of adverse effects is comparable to, or higher than, that associated with equianalgesic doses of epidural morphine. Larger doses (ⱕ50 g) provide analgesia for up to 4 hours.30 Few data are available to evaluate
TABLE 2. Summary of Epidural Opioid Options Opioid
Dose
Duration
Comments
Morphine Fentanyl
3.5-4 mg 50 g
18-24 h Up to 4 h
Sufentanil Meperidine Hydromorphone Methadone Diamorphine
10-20 g 25 mg 1.0 mg 4-5 mg 2.5-5 mg
⬇3 h 2-3 h ⬇12 h 5-6 h ? 5-15 h
“Gold standard” Useful as an intra-operative analgesic Also useful intraoperatively Local anesthetic effects Heroin, not available in U.S.
Reprinted from Palmer CM, D’Angelo R, Paech MJ: Handbook of Obstetric Anesthesia. Oxford, Bios Scientific Publishers, 2002.
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variety of epidural analgesics. The primary aim of this combination is to prolong analgesia, and secondary goals are to decrease the incidence of adverse effects and decrease systemic uptake. Administered with lidocaine, epinephrine results in not only prolonged anesthesia but also in enhanced analgesia (Fig 6). Alpha-2 agonism is likely responsible for most of epinephrine’s intrinsic analgesic properties.38 In parturients, epinephrine may prolong the analgesic effects of shorter-acting opioids.39-42 This prolongation often comes at the expense of an increased incidence or severity of adverse effects. When used as part of a continuous epidural infusion, epinephrine may allow a reduced infusion rate, and consequently, a lower total dose of opioid to be used.
Fig 5. Duration of complete analgesia (visual analog pain score of 0) after doses of epidural fentanyl ranging from 0 to 100 g. Data are mean (standard error). Reprinted with permission from Palmer CM, D’Angelo R, Paech MJ: Handbook of Obstetric Anesthesia. Oxford: Bios Scientific Publishers, 2002. Adapted from Naulty JS, Datta S, Ostheimer GW, et al: Epidural fentanyl for postcesarean delivery pain management. Anesthesiology 63:694-698, 1985.
the risk of respiratory depression. When given IV at these doses, sufentanil can produce profound respiratory depression. Like fentanyl, sufentanil can be used as an intraoperative analgesic, but because of its short duration, it has little value as a postoperative agent.
Other Opioids Speed of onset and duration of analgesia from epidural meperidine (also known as pethidine) increase with dose up to ⬃25 mg; further increasing the dose provides no additional benefit.31 Pain relief lasts ⬃2.5 hours, and although side effects are infrequent, clinical utility is limited by its short duration. Hydromorphone is a semisynthetic derivative of morphine. At a dose of 1.0 mg, analgesia is comparable to 5 mg of epidural morphine, but the duration is considerably shorter (about 12 hours).32 The adverse-effect profile is similar to morphine’s. Epidural methadone has a more rapid onset than epidural morphine, but the duration of analgesia after 4 to 5 mg is only 5 to 6 hours.33 Diamorphine (heroin) has been used as an epidural analgesic, but reports of the duration of analgesia are inconsistent, ranging from 5 to 15 hours after 2.5 to 5 mg.34,35 Among mixed agonist/antagonist opioids, epidural butorphanol has a faster onset but a shorter duration than epidural morphine.36 The low incidence of pruritus after epidural butorphanol is its major advantage, but the short duration and high incidence of somnolence are significant shortcomings. Nalbuphine is another mixed opioid agonist/antagonist. As the dose is increased from 10 to 30 mg, the duration of analgesia increases from ⬃1 to 3 hours.37 Its only significant adverse effect is somnolence, observed in up to 50% of patients after 30 mg. The safety of neuraxial nalbuphine has not been carefully evaluated, however, so its use cannot be recommended.
Nonopioid Analgesics Epinephrine Epinephrine is a naturally occurring catecholamine with both ␣- and -adrenergic agonist actions. It has been used with a
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Clonidine Clonidine is an ␣-adrenergic type-2 receptor agonist. When taken orally, it has significant antihypertensive actions. After epidural or spinal injection, it produces analgesia from activation of ␣-adrenergic receptors within descending inhibitory pathways of the spinal cord (Fig 7). In volunteers, 700 g of epidural clonidine produces significant sedation (Fig 8) and decreased blood pressure.43 At a dose of 150 g, epidural clonidine modestly augments intrathecal morphine analgesia after cesarean section.44 In nonobstetric populations, the addition of clonidine to local anesthetic infusions improves postoperative analgesia, but at the cost of greater sedation and lower blood pressure. Because of these significant adverse effects, it is rarely useful for postcesarean analgesia, and it cannot be recommended.
Summary of Epidural Analgesics There are a variety of ways to provide epidural analgesia after cesarean delivery. Fifty to 100 g of fentanyl mixed with the local anesthetic enhances intraoperative comfort and provides
Fig 6. Epinephrine augmentation of epidural lidocaine anesthesia. When added to epidural lidocaine 1%, sensory block of an electrical stimulus was not merely prolonged, it was enhanced, illustrating epinephrine’s intrinsic analgesic/anesthetic properties. (group P, plain lidocaine 1%; group E, lidocaine 1% with epinephrine 1:200,000). Reprinted with permission from Palmer CM, D’Angelo R, Paech MJ: Handbook of Obstetric Anesthesia. Oxford: Bios Scientific Publishers, 2002. Adapted from Sakura et al.38 CRAIG M. PALMER
Intrathecal Morphine
Fig 7. Descending inhibitory pathway (on right). Neurons with cell bodies in the sensory cortex project caudally, synapsing in the periacquaductal gray matter of the midbrain; this is the location of a high concentration of opioid receptors, and likely a major site of action of systemically administered opioids. Another synapse occurs in the medulla before the pathway terminates in the gray matter of the dorsal lumbar spinal cord. These neurons release norepinephrine, which is an inhibitory neurotransmitter in afferent sensory pathways. Reprinted from Palmer CM, D’Angelo R, Paech MJ: Handbook of Obstetric Anesthesia. Oxford: Bios Scientific Publishers, 2002. After Purves D, Augustine GJ, Fitzpatrick D, et al (eds): Neuroscience. Sunderland, MA: Sinauuer Associates, 1997.
early postoperative analgesia for ⱕ3 hours. Despite the occurrence of minor adverse effects such as pruritus, morphine is still the longest-lasting epidural opioid available, and it is the mainstay of single-injection epidural postoperative analgesia. Although doses used clinically range from 3 to 5 mg, 4 mg seems an optimal dose. For the infrequent patient who requires significantly more analgesics in the early postoperative period, patient-controlled IV analgesia (PCA) is a useful adjunct (see below). Because of the theoretical risk of respiratory depression and the occurrence of adverse effects, standard postoperative orders are very useful for patients receiving epidural morphine (Table 3). Extensive clinical experience with epidural morphine has shown that serious respiratory complications are very rare and conscientiously applied nursing protocols are adequate postoperative monitoring. Nurses should check and record respiratory rates hourly for 12 to 24 hours after epidural morphine. If respiratory rate falls below 8 breaths per minute, then the nurse should immediately inject naloxone and notify the anesthesiologist. In the absence of other sedatives or narcotics, respiratory depression of this degree is extremely uncommon. POSTCESAREAN ANALGESIA
Spinal or subarachnoid anesthesia has enjoyed increased popularity in obstetrics in the last two decades. In many practices, it is more commonly used for cesarean section than epidural anesthesia. As the use of spinal anesthesia has increased, so has the use of intrathecal opioids for postoperative analgesia. As with epidural analgesia, morphine is the mainstay of intrathecal postcesarean analgesia. Intrathecal morphine produces excellent pain relief after cesarean section at surprisingly small doses. When self-administered PCA morphine is used to quantify analgesia, no improvement in analgesia is observed, despite increasing the dose of morphine from 0.1 to 0.5 mg (Fig 9).45 Interestingly, patients will continue to self-medicate with PCA morphine at a constant rate despite a 5- to 10-fold increase in the dose of intrathecal morphine. This suggests that optimal analgesia requires occupation of opioid receptors at two distinct sites within the central nervous system; intrathecal morphine occupies spinal receptors, and parenteral (PCA) morphine acts at supraspinal receptors, perhaps those found in the periaquaductal gray matter of the midbrain. Support for this spinal–supraspinal receptor synergy can be found in animal models.46 Adverse effects after intrathecal morphine are comparable to those observed after epidural morphine. Pruritus occurs in 40% to 80% of patients and appears to be dose dependent (Fig 10). Vomiting occurs rarely after low doses (0.1 mg) of morphine. Clinically significant respiratory depression is rare, but it can occur. At clinically relevant doses, the respiratory response to carbon dioxide challenge is not depressed.47 The dose-response curve of intrathecal morphine is very steep. The optimal dose of intrathecal morphine for postcesarean analgesia lies around 0.1 mg, which provides 18 to 20 hours of good analgesia for most parturients while avoiding excessive adverse effects. As with epidural morphine, standardized postoperative orders are very useful. Intrathecal morphine cannot completely eliminate the need for supplemental analgesics, however, and the best way to insure excellent analgesia may be
Fig 8. Visual analog sedation scores after epidural injection of 700 g of clonidine in nonpregnant volunteers. Reprinted from Palmer CM, D’Angelo R, Paech MJ: Handbook of Obstetric Anesthesia. Oxford: Bios Scientific Publishers, 2002. Adapted from Eisenach et al.43
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TABLE 3. Postoperative Neuraxial Opioid Orders 1. 2. 3. 4. 5. 6.
7. 8. 9. 10.
Epidural/intrathecal , mg, administered at hours on (date) No sedatives or narcotics administered except by order of anesthesiologist One ampule naloxone at bedside at all times Main IV access or heparin-lock at all times Measure and record respiratory rate q 1 h; for respiratory rate ⬍8/min, give naloxone, 0.2 mg IV slowly over 2 min; notify anesthesiologist Supplemental analgesia: Morphine 2 mg IV q 1-2 h PRN -orKetorolac 15 mg IV q 6 h PRN -orIbuprofen 400 mg PO q 6 h PRN For pruritus: nalbuphine, 5 mg IV q 4 h PRN itching For nausea/vomiting: ondansetron 4 mg IV q 6 h PRN nausea and vomiting For pain, pruritus, or nausea/vomiting unresponsive to above, page the anesthesiologist on call This protocol covers 24 h after each dose of neuraxial opioid
through a combination of intrathecal morphine and IV PCA supplementation.
Other Intrathecal Opioids Fentanyl Fentanyl can be used for analgesia at cesarean delivery and the maximal clinical benefit can be obtained with very low doses (5-10 g). The duration of effective analgesia after intrathecal bupivacaine increases from 71.8 minutes without fentanyl to 192 minutes with 6.25 g of fentanyl (Fig 11), but 24-hour supplemental narcotic usage is not affected.48 When added to intrathecal lidocaine anesthesia, fentanyl has similar effects, but the duration of analgesia is shorter.49 The short duration of effective analgesia even at high doses limits the value of intrathecal fentanyl as a postoperative analgesic. Pruritus occurs frequently, but rarely requires treatment, and fentanyl appears to actually decrease the incidence of nausea and vomiting intraoperatively.
Others Subarachnoid sufentanil, up to 10 g, has very similar analgesic properties to fentanyl. Like fentanyl, a short duration limits the
usefulness of sufentanil as a postoperative analgesic.50 Subarachnoid buprenorphine at a dose of 0.045 mg also prolongs the pain-free interval after bupivacaine spinal anesthesia, perhaps as long as 6 to 7 hours. Its only advantage over morphine would seem to be a lower incidence of pruritus.51 Other subarachnoid opioids that have been used in nonpregnant populations include methadone and oxymorphone. Methadone produces analgesia of shorter duration and less consistent quality than morphine, even at doses as high as 20 mg.52 Oxymorphone provides approximately 16 hours of analgesia when administered intrathecally, with predictable adverse effects of pruritus, nausea, and vomiting (Table 4).53 Nalbuphine has been combined with intrathecal morphine to attempt to decrease morphine’s adverse effects. It has no effect on the incidence or severity of pruritus or on postoperative analgesic use, but it tends to increase nausea.
Nonopioid Intrathecal Analgesics Epinephrine may prolong the anesthesia produced by intrathecal local anesthetics. However, the addition of epinephrine to 0.2 mg of intrathecal morphine does not increase the duration of postoperative analgesia or decrease supplemental analgesic requirements after cesarean delivery.54
Conclusion For spinal anesthesia for cesarean delivery, the combination of 0.1 mg of morphine and 10 g of fentanyl with either lidocaine
Fig 9. Mean 24-hour PCA morphine use after doses of intrathecal morphine from 0 to 0.5 mg in parturients after cesarean delivery. Data are mean (standard error). Adapted from Palmer et al.45
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Fig 10. Mean 24-hour pruritus scores in parturients after doses of intrathecal morphine from 0 to 0.5 mg. Adapted from Palmer et al.45 CRAIG M. PALMER
Fig 11. Duration of effective analgesia after intrathecal doses of fentanyl ranging from 0 to 50 g in parturients undergoing cesarean delivery with spinal (subarachnoid) anesthesia. Reprinted with permission from Palmer CM, D’Angelo R, Paech MJ: Handbook of Obstetric Anesthesia. Oxford: Bios Scientific Publishers, 2002. Adapted from Hunt et al.48
or bupivacaine is a good way to insure both intraoperative and postoperative analgesia. Morphine provides 18 to 24 hours of good to excellent postoperative analgesia for most parturients, but if a patient is having significant discomfort, then supplemental analgesia is appropriate. This could be IV PCA morphine, but many parturients are able to take oral analgesics within hours after their surgery, and these medications can be equally effective. Fentanyl may enhance intraoperative comfort and provide some early postoperative analgesia. Because of the very small volumes of opioids used with this technique, it is prudent to measure these drugs in tuberculin syringes to minimize the risk of accidental overdose. As with epidural morphine analgesia, careful postoperative monitoring of patients (respiratory rates) is essential.
Continuous Intrathecal Analgesia Continuous intrathecal analgesia can be used in those patients who have an intrathecal catheter in place. Such a technique allows medications to be titrated to patient comfort and additional boluses given for breakthrough pain. Generally speaking, the highly lipid-soluble opioids, with their fast onset and relatively short duration, are the best-suited agents. A combination of bupivacaine and fentanyl will provide adequate analgesia for most parturients after cesarean delivery (fentanyl 15 g/h with bupivacaine 1.5 mg/h). Sufentanil, 2.5 to 5 g/h, can also be used.55 These options are quite similar to intrathecal analgesics used for labor analgesia, either as infusions or as part of a combined spinal– epidural technique. Intrathecal sufentanil has been associated with significant respiratory depression in a number of patients;56,57 for this reason, closer monitoring, such as continuous pulse oximetry or an intensive care unit, should be used (Table 5).
PCA PCA can be very effective for postcesarean analgesia. Although epidural or intrathecal morphine analgesia is usually rated suPOSTCESAREAN ANALGESIA
perior (by patients) to the analgesia provided by PCA morphine, overall patient satisfaction with PCA is as high, probably because of the feeling of control that PCA provides parturients.58 Both PCA and neuraxial morphine are markedly more effective than intramuscular injections. The choice of opioid for use with PCA does not make any difference in patient satisfaction or adverse effects when equipotent doses are used. Likewise, use of a basal infusion does not change 24-hour opioid usage, but may decrease pain scores with movement. This minor advantage is offset by a higher incidence of nausea.59 Finally, PCA is an excellent choice to use in combination with neuraxial techniques for postcesarean analgesia, and it is an effective way to titrate postoperative analgesia to individual requirements. After initial IV titration of analgesics in the postanesthesia care unit, commonly used PCA regimens would include morphine, 1.5 to 2.0 mg IV q 10 minutes, or meperidine, 10 to 15 mg IV q 8 to 10 minutes. Dosage and time intervals can be adjusted based on individual response.
Epidural PCA Patient-controlled epidural analgesia (PCEA) allows the use of local anesthetics, opioids, and multiple combinations for postoperative analgesia. Compared with single bolus epidural morphine, use of opioid-only PCEA with fentanyl or sufentanil provides comparable analgesia, but the high total doses of opioid used by parturients raise the question of whether the analgesic effects are mediated primarily by systemic uptake or by a true spinal mechanism. As with IV PCA, a basal infusion does not improve the quality of pain relief with PCEA. Background infusions do increase sedation.60 When meperidine is used for PCEA, parturients use ⬃50% less opioid via the PCEA route than the PCA route. Sedation scores are predictably higher with IV PCA (Fig 12).61 Local anesthetics are often added to PCEA for postcesarean analgesia. The concentration of local anesthetic must be low to avoid significant sensory or motor blockade, because many of these patients are ambulatory within hours of surgery. PCEA with fentanyl or buprenorphine plus 0.03% bupivacaine produces effective analgesia, but motor block interferes with ambulation.62 With a lower concentration of bupivacaine (0.01%), ambulation is not affected, but the dose of fentanyl consumed is comparable to that with plain fentanyl PCEA. Thus, it is unclear what benefit including dilute bupivacaine in a PCEA solution provides. Clonidine and epinephrine (which activate ␣-2 adrenergic receptors), and neostigmine (which prevents the breakdown of synaptically released acetylcholine) also have been used with PCEA.63,64 When combined with sufentanil PCEA, both epinephrine and clonidine significantly reduce epidural opioid use. Unfortunately, clonidine significantly decreases blood
TABLE 4. Summary of Intrathecal Opioid Options Opioid
Dose
Duration
Morphine Fentanyl Sufentanil Buprenorphine Methadone Oxymorphine
0.1-0.2 mg 5-10 g Up to 5 g Limited experience; doses and durations not well characterized; subarachnoid (spinal) use not recommended
18-24 h 3-4 h 3-4 h
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TABLE 5. Continuous Intrathecal Analgesia Medications
Initial Bolus
Infusion
Comments
Sufentanil Fentanyl/bupivacaine
5 g Fentanyl 25 g with bupivacaine 2.5 mg
2.5-5 g/h Fentanyl 15 g/h bupivacaine 1.5 mg/h
Mix as 1 g/mL infusion Mix infusion with fentanyl 5 g and bupivacaine 0.5 mg per mL run at 3 mL/h*
*To mix infusion: Begin with 50 mL of normal saline; withdraw 15 mL; add 5 mL of .5% bupivacaine and 5 mL of fentanyl. Note: Most commercial infusion bags are slightly overfilled, therefore these numbers are only approximations.
pressure and heart rate, and neostigmine, even at very low doses, significantly increases nausea and vomiting. These adverse effects have limited the clinical utility of both clonidine and neostigmine. Clearly, PCEA can be an effective technique for postcesarean analgesia. Whether it offers distinct advantages over epidural or intrathecal morphine is a matter of dispute. A disadvantage is the necessity to maintain a functioning epidural catheter in the postoperative period. Furthermore, in many practices cesarean delivery is more likely to be accomplished with spinal than with epidural anesthesia, which precludes the technique. It remains a useful technique for selected patients and populations.
Nonsteroidal Agents Nonsteroidal anti-inflammatory drugs (NSAIDs) may be of value in this population. As noted above, despite the good quality of analgesia available with neuraxial techniques, supplemental analgesia is sometimes necessary, and NSAIDs (both oral and parenteral) are useful adjuncts to epidural or intrathecal morphine. Also, if patients have oral intake restricted for some time after delivery, then a parenteral NSAID can be used as an alternative to oral medications for supplemental analgesia. NSAIDs lack the potency to provide complete analgesia after a cesarean delivery. Thirty mg of ketorolac is roughly comparable to 75 mg of meperidine (intramuscular dosing), but analgesia after ketorolac is inconsistent and of short duration.65 When administered via continuous IV infusion, diclofenac or ketoprofen decrease postoperative opioid requirements by about 40% when compared with placebo.66 Studies of NSAIDs as adjuncts to neuraxial morphine have shown inconsistent results. Although in some situations NSAIDs can decrease postoperative opioid use, at this point it is premature to make a blanket recommendation regarding their use.
Fig 12. A comparison of pain scores between IV PCA and PCEA with meperidine after cesarean delivery. The solid line represents the period parturients received PCEA and the dashed line represents the period they received IV PCA in this blinded, crossover study. Reprinted with permission from Palmer CM, D’Angelo R, Paech MJ: Handbook of Obstetric Anesthesia. Oxford: Bios Scientific Publishers, 2002. Adapted from Paech et al.61
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Conclusion Cesarean delivery is probably the most common major surgical procedure performed in the world today. This huge number of anesthetics being performed in a remarkably homogeneous population (all being female, relatively young, and usually healthy) has allowed analgesic options to be systematically evaluated. Given current understanding of analgesic dose-response relationships, planning a cesarean anesthetic should include planning for postoperative analgesia. The variety of available options means there is an effective technique for every patient.
References 1. Martin WR, Eades CG, Thompson JA: The effects of morphine- and nalorphine-like drugs in the nondependent and morphine-dependent chronic spinal dog. J Pharmacol Exp Ther 198:66-82, 1976 2. Lord JAH, Waterfield AA, Hughes J: Endogenous opioid peptides: multiple agonists and receptors. Nature 267:495-499, 1977 3. Yaksh TL, Rudy TA: Studies on the direct spinal action of narcotics in the production of analgesia in the rat. J Pharmacol Exp Ther 202:411-428, 1977 4. Behar M, Magora F, Olshwang D: Epidural morphine in treatment of pain. Lancet 1:527-529, 1979 5. Youngstrom PC, Cowan RI, Sutheimer C: Pain relief and plasma concentrations from epidural and intramuscular morphine in postcesarean patients. Anesthesiology 57:404-409, 1982 6. Kotelko DM, Dailey PA, Shnider SM: Epidural morphine analgesia after cesarean delivery. Obstet Gynecol 63:409-413, 1984 7. Writer WDR, Hurtig JB, Evans D, et al. Epidural morphine prophylaxis of postoperative pain: report of a double-blind multicentre study. Can Anaesth Soc J 32:330-338, 1985 8. Rosen MA, Hughes SC, Shnider SM: Epidural morphine for the relief of postoperative pain after cesarean delivery. Anesth Analg 62:666672, 1983 9. Palmer CM, Nogami WM, Van Maren G, et al: Post-cesarean epidural morphine: a dose response study. Anesth Analg 90:887-891, 2000 10. Asantila R, Eklund P, Rosenberg PH: Epidural analgesia with 4 mg of morphine following caesarean section: effect of injected volume. Acta Anaesthesiol Scand 37:764-767, 1993 11. Ballantyne JC, Loach AB, Carr DB: Itching after epidural and spinal opiates. Pain 33:149-160, 1988 12. Kam PC, Tan KH: Pruritus—itching for a cause and relief? Anaesthesia 51:1133-1138, 1996 13. Fuller JG, McMorland GH, Douglas J: Epidural morphine for postoperative pain after caesarean section: a report of 4880 patients. Can J Anaesth 37:636-640, 1990 14. Gourlay GK, Cherry DA, Cousins MJ: Cephalad migration of morphine in CSF following lumbar epidural administration in patients with cancer pain. Pain 23:317, 1985 15. Drayer BP, Rosenbaum AE: Studies of the third circulation, amipaque CT cisternography and ventriculography. J Neurosurg 48:946-956, 1978 16. Leicht CH, Hughes SC, Dailey PA: Epidural morphine sulfate for analgesia after cesarean section: a prospective report of 1000 patients. Anesthesiology 65:A366, 1986 17. Gieraerts R, Navalgund A, Vaes L: Increased incidence of itching and herpes simplex in patients given epidural morphine after cesarean section. Anesth Analg 66:1321-1324, 1987 CRAIG M. PALMER
18. Crone LA, Conly JM, Clark KM: Recurrent herpes simplex virus labialis and the use of epidural morphine in obstetric patients. Anesth Analg 67:318-323, 1988 19. Norris MC, Weiss JH, Carney M: Incidence of recurrent herpes simplex virus labialis after cesarean section. Intl J Obstet Anesth 3:127-131, 1994 20. Wang JJ, Ho ST, Hu OY: Comparison of intravenous nalbuphine infusion versus saline as an adjuvant for epidural morphine. Reg Anesth 21:214-218, 1996 21. Henderson SK, Cohen H: Nalbuphine augmentation of analgesia and sreversal of side effects following epidural hydromorphone. Anesthesiology 65:216-218, 1986 22. Warwick JP, Kearns CF, Scott WE: The effect of subhypnotic doses of propofol on the incidence of pruritus after intrathecal morphine for caesarean section. Anaesthesia 52:270-275, 1997 23. Horta ML, Horta BL: Inhibition of epidural morphine-induced pruritus by intravenous droperidol. Reg Anesth 18:118-120, 1993 24. Larijani GE, Goldberg ME, Rogers KH: Treatment of opioid-induced pruritus with ondansetron: report of four patients. Pharmacotherapy 16:958-960, 1996 25. Abboud TK, Lee K, Zhu J: Prophylactic oral naltrexone with intrathecal morphine for cesarean section: effects on adverse reactions and analgesia. Anesth Analg 71:367-370, 1990 26. Kendrick WD, Woods AM, Daly MY: Naloxone versus nalbuphine infusion for prophylaxis of epidural morphine-induced pruritus. Anesth Analg 82:641-647, 1996 27. Gambling DR, Howell P, Huber C, et al: Epidural butorphanol does not reduce side effects from epidural morphine after cesarean birth. Anesth Analg 78:1099-1104, 1994 28. Kotelko DM, Rottman RL, Wright WC, et al: Transdermal scopolamine decreases nausea and vomiting following cesarean section in patients receiving epidural morphine. Anesthesiology 71:675-678, 1989 29. Naulty JS, Datta S, Ostheimer GW: Epidural fentanyl for postcesarean delivery pain management. Anesthesiology 63:694-698, 1985 30. Cohen SE, Tan S, White PF: Sufentanil analgesia following cesarean section: epidural versus intravenous administration. Anesthesiology 68:129-134, 1988 31. Ngan Kee WD, Lam KK, Chen PP, et al: Epidural meperidine after cesarean section. Anesthesiology 85:289-294, 1996 32. Halpern SH, Arellano R, Preston R, et al: Epidural morphine vs hydromorphone in post-caesarean section patients. Can J Anaesth 43:595-598, 1996 33. Beeby D, MacIntosh KC, Bailey M, et al: Postoperative analgesia for caesarean section using epidural methadone. Anaesthesia 39:61-63, 1984 34. Haynes SR, Davidson I, Allsop JR, et al: Comparison of epidural methadone with epidural diamorphine for analgesia following caesarean section. Acta Anaesthesiol Scand 37:375-380, 1993 35. Roulson BJ, Bennett J, Shaw M, et al: Effect of extradural diamorphine on analgesia after caesarean section under subarachnoid block. Br J Anaesth 71:810-813, 1993 36. Abboud TK, Moore M, Zhu J: Epidural butorphanol or morphine for the relief of section pain: ventilatory responses to carbon dioxide. Anesth Analg 66:887-893, 1987 37. Camann WR, Hurley RH, Gilbertson LI, et al: Epidural nalbuphine for analgesia following caesarean delivery: dose-response and effect of local anaesthetic choice. Can J Anaesth 38:728-732, 1991 38. Sakura S, Sumi M, Morimoto N: The addition of epinephrine increases the intensity of sensory block during epidural anesthesia with lidocaine. Reg Anesth Pain Med 24:541-546, 1999 39. Robertson K, Douglas MJ, McMorland GH: Epidural fentanyl, with and without epinephrine for post-caesarean section analgesia. Can Anaesth Soc J 32:502-505, 1985 40. Collins JG, Kitahata LM, Matsumoto M, et al: Spinally administered epinephrine suppresses noxiously evoked activity of WDR neurons in the dorsal horn of the spinal cord. Anesthesiology 60:269-275, 1984 41. Leicht CH, Kelleher AJ, Robinson DE, et al: Prolongation of postoperative epidural sufentanil analgesia with epinephrine. Anesth Analg 70:323-325, 1990 42. McMorland GH, Douglas MJ, Kim JH, et al: Epidural sufentanil for post-caesarean section analgesia: lack of benefit of epinephrine. Can J Anaesth 37:432-437, 1990
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43. Eisenach J, Detweiler D, Hood D: Hemodynamic and analgesic actions of epidurally administered clonidine. Anesthesiology 78:277287, 1993 44. Massone ML, Lampugnani E, Calevo MG: The effects of a dose of epidural clonidine combined with intrathecal morphine for postoperative analgesia. Minerva Anestesiol 64:289-296, 1998 45. Palmer CM, Emerson S, Voulgaropoulos D, et al: Dose-response relationship of intrathecal morphine for post-cesarean analgesia. Anesthesiology 90:437-444, 1999 46. Yeung JC, Rudy TA: Multiplicative interaction between narcotic agonisms expressed at spinal and supraspinal sites of antinociceptive action as revealed by concurrent intrathecal and intracerebroventricular injections of morphine. J Pharmacol Exp Ther 215:633642, 1980 47. Abouleish E, Rawal N, Rashad MN: The addition of 0.2 mg subarachnoid morphine to hyperbaric bupivacaine for cesarean delivery: a prospective study of 856 cases. Reg Anesth 16:137-140, 1991 48. Hunt CO, Naulty JS, Bader AM: Perioperative analgesia with subarachnoid fentanyl-bupivacaine for cesarean delivery. Anesthesiology 71:535-540, 1989 49. Palmer CM, Voulgaropoulos D, Alves D: Subarachnoid fentanyl augments lidocaine spinal anesthesia for cesarean delivery. Reg Anesth 20:389-394, 1995 50. De Sousa H, De la Vega S: Spinal sufentanil. Reg Anesth 13:23, 1988 51. Cellano D, Capogna G: Spinal buprenorphine for postoperative analgesia after caesarean section. Acta Anaesthesiol Scand 33:236238, 1989 52. Jacobson L, Chabal C, Brody MC: Intrathecal methadone and morphine for postoperative analgesia: a comparison of the efficacy, duration and side effects. Anesthesiology 69:A352, 1988 53. De Sousa H, Klein E: Intrathecal and epidural oxymorphone. Anesthesiology 71:A699, 1989 54. Abouleish E, Rawal N, Tobon–Randall B, et al: A clinical and laboratory study to compare the addition of 0.2 mg of morphine, 0.2 mg of epinephrine, or their combination to hyperbaric bupivacaine for spinal anesthesia in cesarean section. Anesth Analg 77:457-462, 1993 55. Palmer CM: Continuous intrathecal sufentanil for postoperative analgesia. Anesth Analg 92:244-245, 2001 56. Hays RL, Palmer CM: Respiratory depression after intrathecal sufentanil for labor. Anesthesiology 81:511-512, 1994 57. Ferouz F, Norris MC, Leighton BL: Risk of respiratory arrest after intrathecal sufentanil. Anesth Analg 85:1088-1090, 1997 58. Eisenach JC, Grice SC, Dewan DM: Patient-controlled analgesia following cesarean section: a comparison with epidural and intramuscular narcotics. Anesthesiology 68:444-448, 1988 59. Sinatra R, Chung KS, Silverman DG: An evaluation of morphine and oxymorphone administered via patient-controlled analgesia (PCA) or PCA plus basal infusion in postcesarean delivery patient. Anesthesiology 71:502, 1989 60. Vercauteren MP, Coppejans HC, Broecke PWT, et al: Epidural sufentanil for postoperative patient-controlled analgesia (PCA) with or without background infusion: a double-blind comparison. Anesth Analg 80:76-80, 1995 61. Paech MJ, Moore JS, Evans SF: Meperidine for patient-controlled analgesia after cesarean section. Anesthesiology 80:1268-1276, 1994 62. Cohen S, Amar D, Pantuck CB, et al: Adverse effects of epidural 0.03% bupivacaine during analgesia after cesarean section. Anesth Analg 75:753-756, 1992 63. Paech MJ, Pavy TJG, Orlikowski CEP: Postoperative epidural infusion: a randomized, double-blind, dose-finding trial of clonidine in combination with bupivacaine and fentanyl. Anesth Analg 84:13231328, 1997 64. Vercauteren MP, Vandeput DM, Meert TF, et al: Patient-controlled epidural analgesia with sufentanil following caesarean section: the effect of adrenaline and clonidine admixture. Anaesthesia 49:767771, 1994 65. Cohen SE, Desai JB, Ratner EF: Ketorolac and spinal morphine for postcesarean analgesia. Intl J Obstet Anesth 5:14-18, 1996 66. Rorarius MGF, Suominen P, Baer GA, et al: Diclofenac and ketoprofen for pain treatment after elective caesarean section. Br J Anaesth 70:293-297, 1993
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There are a variety of effective options for postcesarean analgesia. A single epidural injection of 4 mg of morphine provides 18 to 24 hours of good to excellent analgesia. A single spinal injection of 0.1 mg of morphine also provides 18 to 24 hours of analgesia. Continuous epidural catheter techniques can be effective, usually by relying on a combination of a short-acting opioid, such as fentanyl or sufentanil, and a local anesthetic, usually bupivacaine or ropivacaine. Occasionally, with this technique, motor block caused by the local anesthetic interferes with maternal ambulation. Patient-controlled techniques, either intravenous or epidural, also have proven effective. A variety of opioids (including morphine, meperidine, and fentanyl) have been used for intravenous patient-controlled analgesia with little to recommend one drug over the other. For epidural patientcontrolled analgesia, opioid–local anesthetic combinations are usually used, with delivery parameters dependent on the exact concentration of the chosen solution. Regardless of the technique chosen, careful monitoring of patients in the early postoperative period (24 hours) is essential to avoid adverse effects and to ensure maternal satisfaction. © 2003 Elsevier Inc. All rights reserved.
esarean delivery is the most frequently performed inpatient operation in the United States and probably throughout the world. In the last two decades, our improved understanding of central nervous system pharmacology and improvements in technology have changed the way we provide postoperative analgesia in both obstetric and surgical patients. For many years, intramuscular narcotics were the mainstay of analgesia after cesarean delivery; in some settings, they still are. Today, considering our knowledge of and experience with postoperative pain management in this population, planning an anesthetic for cesarean delivery also should include planning for adequate postoperative analgesia.
C
Epidural Morphine Though the idea that cell-membrane receptors can mediate drug effects was first postulated in the 1800’s, only in the last few decades has substantial progress been made in the area of receptor pharmacology. By the mid-1970’s, two subtypes of opioid receptors, mu and kappa, had been described and characterized.1 A third opioid-receptor subtype, the delta receptor, was described shortly thereafter.2 In 1975, enkephalins, a form of endogenous opioid, were isolated and characterized. By the From the Department of Anesthesiology, University of Arizona Health Sciences Center, Tucson, AZ. Address reprint requests to: Craig M. Palmer, MD, Department of Anesthesiology, University of Arizona Health Sciences Center, P.O. Box 245114, Tucson, AZ 85724. © 2003 Elsevier Inc. All rights reserved. 1084-208X/03/0704-0007$30.00/0 doi:10.1016/S1084-208X(03)00039-9
late 1970’s, autoradiographic mapping had revealed opioidreceptor distribution within the central nervous system. High concentrations of opioid receptors are found in the substantia gelatinosa of the spinal cord, the medullary dorsal horn, and periaquaductal gray matter of the midbrain (Fig 1). In 1977, intrathecal morphine was demonstrated to produce high-quality, naloxone-reversible analgesia in the rat.3 By 1979, epidural morphine was reported to be an effective analgesic in cancer patients.4 Shortly thereafter, a number of series reported epidural morphine provided effective postcesarean analgesia in doses ranging from 2 to 10 mg.5-8 Morphine is the most widely used epidural opioid for analgesia after cesarean section. Pain relief from epidural morphine for postcesarean analgesia follows a consistent dose-response relationship.9 As the dose of epidural morphine increases, analgesia improves until the dose reaches about 4 mg (Figs 2 and 3). This dose provides 18 to 24 hours of good to excellent analgesia. Increasing the dose above 4 mg does not further improve analgesia, but does increase the frequency and severity of adverse effects. Volume of diluent is not a major factor in epidural morphine analgesia; a volume of 5 to 10 mL is generally adequate.10 Because of interindividual differences, some patients will require additional analgesics (see below). A higher failure rate (ie, diminished analgesia) becomes apparent when using less than 3 mg of epidural morphine.
Adverse Effects of Epidural Morphine Pruritus Although an effective analgesic, epidural morphine does have significant adverse effects, with pruritus being the most common. Pruritus characteristically occurs on the face or trunk, although it may be generalized. In the clinically used range, pruritus is not significantly dose-related (Fig 4).9 The exact mechanism by which epidural morphine causes pruritus is unknown.11,12 The available evidence indicates it to be more complex than a simple receptor-related issue. The role of opioid receptors in pruritus may primarily be via facilitation of other excitatory neuronal pathways and protective reflexes. A full understanding of the phenomenon awaits further investigation.
Nausea and Vomiting Nausea and vomiting are infrequent after epidural morphine. In some series, the reported incidence ranges from 11% to about 30%,6,13 but others have found the incidence to be no different than placebo.9 Epidural morphine can cause nausea and vomiting by stimulating the chemoreceptor trigger zone located in the base of the fourth ventricle of the brain. Morphine, which is highly hydrophilic, remains free (unbound) in the cerebrospinal fluid for a significantly longer time than more lipophilic opioids (ie, fentanyl or sufentanil). Morphine concentration in cervical cerebrospinal fluid peaks 3 to 4 hours after injection.14
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Fig 1. The dorsal horn of the lumbar spinal cord. Afferent sensation is carried primarily by Type C and A neurons, which synapse primarily in Lamina II, the substantia gelatinosa. Opioid receptors (the small squares in the cell membranes) are located presynaptically on type C fibers, but not type A fibers; they are also located postsynaptically on interneurons and projection neurons. About 75% of opioid receptors are located presynaptically, with ⬃25% postsynaptically.
Radiographic studies of other water-soluble compounds confirm that cephalad migration in the cerebrospinal fluid does occur.15
Respiratory Depression Shortly after its introduction to clinical use, respiratory depression was recognized as a complication of epidural morphine. The risk at clinically used doses is quite low, however. A retrospective review of 4,880 parturients receiving epidural morphine after cesarean delivery found a respiratory rate below 10 in only 12 patients, or 0.25%.13 A prospective study of 1,000
Fig 2. Twenty-four-hour PCA morphine use after varying doses of epidural morphine. Data are mean (ⴞSEM) Reprinted with permission from Palmer CM, D’Angelo R, Paech MJ: Handbook of Obstetric Anesthesia. Oxford: Bios Scientific Publishers, 2002. Adapted from Palmer CM, Nogami WM, Van Maren G, et al: Postcesarean epidural morphine: a dose response study. Anesth Analg 90:887-891, 2000.
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Fig 3. Cumulative PCA morphine use after varying doses of epidural morphine. Data are mean (ⴞSEM), and are slightly offset for clarity. Reprinted with permission from Palmer CM, D’Angelo R, Paech MJ: Handbook of Obstetric Anesthesia. Oxford: Bios Scientific Publishers, 2002. Adapted from Palmer CM, Nogami WM, Van Maren G, et al: Postcesarean epidural morphine: a dose response study. Anesth Analg 90:887-891, 2000.
parturients who received morphine, 5 mg epidurally, reported 4 patients with a respiratory rate of below 10 (0.4%).16 The incidence of clinically significant respiratory depression after epidural morphine at doses of 5 mg or less in the obstetric population is at most 0.2% to 0.3%. Respiratory depression after epidural morphine is usually described as “late,” with an onset between 6 and 12 hours after administration. This “delayed” depression is caused by the slow cephalad migration of epidurally administered morphine, which can cause direct central depression of respiration. Untreated, a gradual decline in respiratory rate leads to progressive respiratory acidosis. Based on case reports, the risk of respiratory depression probably rises as the dose increases, at least
Fig 4. Cumulative 24-hour pruritus scores after varying doses of epidural morphine. Data are mean (standard error). *Itching in the control group (group 0) was significantly lower than the 4 epidural morphine groups, which were not different from each other. Reprinted with permission from Palmer CM, D’Angelo R, Paech MJ: Handbook of Obstetric Anesthesia. Oxford: Bios Scientific Publishers, 2002. Adapted from Palmer CM, Nogami WM, Van Maren G, et al: Postcesarean epidural morphine: a dose response study. Anesth Analg 90:887-891, 2000. CRAIG M. PALMER
TABLE 1. Side Effects of Neuraxial Morphine Side Effect
Incidence
Treatment
Comments
Pruritus
Up to 90-100%
Usually mild; Naloxone rarely necessary
Nausea and vomiting
Probably ⬍10%
Respiratory depression
⬍0.25%
Nalbuphine 5 mg IV Or diphenhydramine 12.5-25 mg IV Or naloxone 0.04-0.2 mg IV Ondansetron 4 mg IV or droperidol 0.625 mg IV Naloxone 0.2-0.4 mg IV. Assisted ventilation if necessary
beyond 5 mg. Other factors such as obesity and the concomitant administration of other narcotics also increase the risk. Early respiratory depression after epidural morphine also is possible. This event probably arises from rapid systematic uptake or intravascular injection of the drug.
Herpes Simplex Labialis In 1987, Gieraerts et al17 reported the results of a prospective, nonrandomized study of 44 parturients after cesarean delivery. Twenty-six of these patients received epidural morphine at surgery, and up to twice daily thereafter. Another 18 women received intramuscular morphine. Recurrent herpes simplex labialis lesions appeared in 9 of the 26 patients in the epidural group but in none of the patients in the intramuscular group. A later retrospective study15 corroborated their report, finding herpes simplex labialis lesions recurred in 9.7% of patients who received epidural morphine but in only 0.6% of those who did not. Other investigators have been unable to verify this association. Norris et al19 found no differences in the incidence of recurrent herpes simplex labialis among 203 parturients receiving various anesthetics for cesarean section, with or without neuraxial morphine. These disparate findings may represent differences in the study populations, which have not yet been characterized, or other unrecognized factors.
Treatment of Adverse Effects (Table 1) Nalbuphine (5 mg intravenously [IV]) is an effective treatment for pruritus, does not reverse analgesia, and has no significant adverse effects.20,21 It is an excellent first-line choice should treatment be necessary. Diphenhydramine, 12.5 to 25 mg IV, also usually provides adequate symptomatic relief, but the associated sedation may be as instrumental in providing relief as its antihistaminergic effect. In rare cases, naloxone may be necessary to relieve severe pruritus (0.04-0.2 mg IV, followed by a continuous infusion; start at 0.4 to 0.6 mg/h and titrate as needed). Other treatments, including propofol, droperidol, and ondansetron have been reported effective in treating pruritus, but are generally either too costly for routine use or have significant adverse effects themselves.22-24 Treatment options for nausea and vomiting include antiemetics and opioid antagonists. As noted above, nausea and vomiting in this setting are usually not caused by the epidural morphine, and conventional antiemetics should be the first option. Four mg of IV ondansetron or 0.625 mg of droperidol are generally effective treatments. IV nalbuphine at 5 to 10 mg or very low-dose naloxone can relieve nausea and vomiting if it is secondary to epidural morphine. Early or late, the treatment of choice for respiratory depresPOSTCESAREAN ANALGESIA
Usually not related to epidural morphine Very rare in healthy parturients
sion is IV naloxone. Institute artificial or mechanical support of ventilation immediately if the patient is obtunded while waiting for naloxone to take effect. Preemptive therapy to prevent the adverse effects of epidural morphine has been largely disappointing. Although a number of treatments can prevent adverse effects, they generally also either decrease analgesia or cause adverse effects of their own. IV naloxone and oral naltrexone25,26 can prevent adverse effects, but both decrease analgesia in a dose-dependent fashion. Epidural butorphanol modestly decreases adverse effects, but causes somnolence.27 Prophylactic transdermal scopolamine decreases the incidence of nausea and vomiting during the first 24 hours after cesarean delivery, but it must be applied several hours in advance and it causes dry mouth.28 For these reasons, prophylactic treatment is rarely recommended.
Other Epidural Opioids (Table 2) Fentanyl Epidural fentanyl, 50 to 100 g, rapidly provides profound analgesia for up to 4 hours (Fig 5).29 Higher doses neither improve nor prolong pain relief. Epidural fentanyl causes the same adverse effects as morphine, although onset is faster and duration is shorter. Intraoperatively, epidural fentanyl improves patient comfort and may decrease the incidence of nausea and vomiting. Although useful intraoperatively during epidural anesthesia for cesarean delivery, the duration of epidural fentanyl limits its utility as a postoperative analgesic.
Sufentanil The only advantage of epidural sufentanil over epidural morphine is its rapid onset. The incidence of adverse effects is comparable to, or higher than, that associated with equianalgesic doses of epidural morphine. Larger doses (ⱕ50 g) provide analgesia for up to 4 hours.30 Few data are available to evaluate
TABLE 2. Summary of Epidural Opioid Options Opioid
Dose
Duration
Comments
Morphine Fentanyl
3.5-4 mg 50 g
18-24 h Up to 4 h
Sufentanil Meperidine Hydromorphone Methadone Diamorphine
10-20 g 25 mg 1.0 mg 4-5 mg 2.5-5 mg
⬇3 h 2-3 h ⬇12 h 5-6 h ? 5-15 h
“Gold standard” Useful as an intra-operative analgesic Also useful intraoperatively Local anesthetic effects Heroin, not available in U.S.
Reprinted from Palmer CM, D’Angelo R, Paech MJ: Handbook of Obstetric Anesthesia. Oxford, Bios Scientific Publishers, 2002.
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variety of epidural analgesics. The primary aim of this combination is to prolong analgesia, and secondary goals are to decrease the incidence of adverse effects and decrease systemic uptake. Administered with lidocaine, epinephrine results in not only prolonged anesthesia but also in enhanced analgesia (Fig 6). Alpha-2 agonism is likely responsible for most of epinephrine’s intrinsic analgesic properties.38 In parturients, epinephrine may prolong the analgesic effects of shorter-acting opioids.39-42 This prolongation often comes at the expense of an increased incidence or severity of adverse effects. When used as part of a continuous epidural infusion, epinephrine may allow a reduced infusion rate, and consequently, a lower total dose of opioid to be used.
Fig 5. Duration of complete analgesia (visual analog pain score of 0) after doses of epidural fentanyl ranging from 0 to 100 g. Data are mean (standard error). Reprinted with permission from Palmer CM, D’Angelo R, Paech MJ: Handbook of Obstetric Anesthesia. Oxford: Bios Scientific Publishers, 2002. Adapted from Naulty JS, Datta S, Ostheimer GW, et al: Epidural fentanyl for postcesarean delivery pain management. Anesthesiology 63:694-698, 1985.
the risk of respiratory depression. When given IV at these doses, sufentanil can produce profound respiratory depression. Like fentanyl, sufentanil can be used as an intraoperative analgesic, but because of its short duration, it has little value as a postoperative agent.
Other Opioids Speed of onset and duration of analgesia from epidural meperidine (also known as pethidine) increase with dose up to ⬃25 mg; further increasing the dose provides no additional benefit.31 Pain relief lasts ⬃2.5 hours, and although side effects are infrequent, clinical utility is limited by its short duration. Hydromorphone is a semisynthetic derivative of morphine. At a dose of 1.0 mg, analgesia is comparable to 5 mg of epidural morphine, but the duration is considerably shorter (about 12 hours).32 The adverse-effect profile is similar to morphine’s. Epidural methadone has a more rapid onset than epidural morphine, but the duration of analgesia after 4 to 5 mg is only 5 to 6 hours.33 Diamorphine (heroin) has been used as an epidural analgesic, but reports of the duration of analgesia are inconsistent, ranging from 5 to 15 hours after 2.5 to 5 mg.34,35 Among mixed agonist/antagonist opioids, epidural butorphanol has a faster onset but a shorter duration than epidural morphine.36 The low incidence of pruritus after epidural butorphanol is its major advantage, but the short duration and high incidence of somnolence are significant shortcomings. Nalbuphine is another mixed opioid agonist/antagonist. As the dose is increased from 10 to 30 mg, the duration of analgesia increases from ⬃1 to 3 hours.37 Its only significant adverse effect is somnolence, observed in up to 50% of patients after 30 mg. The safety of neuraxial nalbuphine has not been carefully evaluated, however, so its use cannot be recommended.
Nonopioid Analgesics Epinephrine Epinephrine is a naturally occurring catecholamine with both ␣- and -adrenergic agonist actions. It has been used with a
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Clonidine Clonidine is an ␣-adrenergic type-2 receptor agonist. When taken orally, it has significant antihypertensive actions. After epidural or spinal injection, it produces analgesia from activation of ␣-adrenergic receptors within descending inhibitory pathways of the spinal cord (Fig 7). In volunteers, 700 g of epidural clonidine produces significant sedation (Fig 8) and decreased blood pressure.43 At a dose of 150 g, epidural clonidine modestly augments intrathecal morphine analgesia after cesarean section.44 In nonobstetric populations, the addition of clonidine to local anesthetic infusions improves postoperative analgesia, but at the cost of greater sedation and lower blood pressure. Because of these significant adverse effects, it is rarely useful for postcesarean analgesia, and it cannot be recommended.
Summary of Epidural Analgesics There are a variety of ways to provide epidural analgesia after cesarean delivery. Fifty to 100 g of fentanyl mixed with the local anesthetic enhances intraoperative comfort and provides
Fig 6. Epinephrine augmentation of epidural lidocaine anesthesia. When added to epidural lidocaine 1%, sensory block of an electrical stimulus was not merely prolonged, it was enhanced, illustrating epinephrine’s intrinsic analgesic/anesthetic properties. (group P, plain lidocaine 1%; group E, lidocaine 1% with epinephrine 1:200,000). Reprinted with permission from Palmer CM, D’Angelo R, Paech MJ: Handbook of Obstetric Anesthesia. Oxford: Bios Scientific Publishers, 2002. Adapted from Sakura et al.38 CRAIG M. PALMER
Intrathecal Morphine
Fig 7. Descending inhibitory pathway (on right). Neurons with cell bodies in the sensory cortex project caudally, synapsing in the periacquaductal gray matter of the midbrain; this is the location of a high concentration of opioid receptors, and likely a major site of action of systemically administered opioids. Another synapse occurs in the medulla before the pathway terminates in the gray matter of the dorsal lumbar spinal cord. These neurons release norepinephrine, which is an inhibitory neurotransmitter in afferent sensory pathways. Reprinted from Palmer CM, D’Angelo R, Paech MJ: Handbook of Obstetric Anesthesia. Oxford: Bios Scientific Publishers, 2002. After Purves D, Augustine GJ, Fitzpatrick D, et al (eds): Neuroscience. Sunderland, MA: Sinauuer Associates, 1997.
early postoperative analgesia for ⱕ3 hours. Despite the occurrence of minor adverse effects such as pruritus, morphine is still the longest-lasting epidural opioid available, and it is the mainstay of single-injection epidural postoperative analgesia. Although doses used clinically range from 3 to 5 mg, 4 mg seems an optimal dose. For the infrequent patient who requires significantly more analgesics in the early postoperative period, patient-controlled IV analgesia (PCA) is a useful adjunct (see below). Because of the theoretical risk of respiratory depression and the occurrence of adverse effects, standard postoperative orders are very useful for patients receiving epidural morphine (Table 3). Extensive clinical experience with epidural morphine has shown that serious respiratory complications are very rare and conscientiously applied nursing protocols are adequate postoperative monitoring. Nurses should check and record respiratory rates hourly for 12 to 24 hours after epidural morphine. If respiratory rate falls below 8 breaths per minute, then the nurse should immediately inject naloxone and notify the anesthesiologist. In the absence of other sedatives or narcotics, respiratory depression of this degree is extremely uncommon. POSTCESAREAN ANALGESIA
Spinal or subarachnoid anesthesia has enjoyed increased popularity in obstetrics in the last two decades. In many practices, it is more commonly used for cesarean section than epidural anesthesia. As the use of spinal anesthesia has increased, so has the use of intrathecal opioids for postoperative analgesia. As with epidural analgesia, morphine is the mainstay of intrathecal postcesarean analgesia. Intrathecal morphine produces excellent pain relief after cesarean section at surprisingly small doses. When self-administered PCA morphine is used to quantify analgesia, no improvement in analgesia is observed, despite increasing the dose of morphine from 0.1 to 0.5 mg (Fig 9).45 Interestingly, patients will continue to self-medicate with PCA morphine at a constant rate despite a 5- to 10-fold increase in the dose of intrathecal morphine. This suggests that optimal analgesia requires occupation of opioid receptors at two distinct sites within the central nervous system; intrathecal morphine occupies spinal receptors, and parenteral (PCA) morphine acts at supraspinal receptors, perhaps those found in the periaquaductal gray matter of the midbrain. Support for this spinal–supraspinal receptor synergy can be found in animal models.46 Adverse effects after intrathecal morphine are comparable to those observed after epidural morphine. Pruritus occurs in 40% to 80% of patients and appears to be dose dependent (Fig 10). Vomiting occurs rarely after low doses (0.1 mg) of morphine. Clinically significant respiratory depression is rare, but it can occur. At clinically relevant doses, the respiratory response to carbon dioxide challenge is not depressed.47 The dose-response curve of intrathecal morphine is very steep. The optimal dose of intrathecal morphine for postcesarean analgesia lies around 0.1 mg, which provides 18 to 20 hours of good analgesia for most parturients while avoiding excessive adverse effects. As with epidural morphine, standardized postoperative orders are very useful. Intrathecal morphine cannot completely eliminate the need for supplemental analgesics, however, and the best way to insure excellent analgesia may be
Fig 8. Visual analog sedation scores after epidural injection of 700 g of clonidine in nonpregnant volunteers. Reprinted from Palmer CM, D’Angelo R, Paech MJ: Handbook of Obstetric Anesthesia. Oxford: Bios Scientific Publishers, 2002. Adapted from Eisenach et al.43
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TABLE 3. Postoperative Neuraxial Opioid Orders 1. 2. 3. 4. 5. 6.
7. 8. 9. 10.
Epidural/intrathecal , mg, administered at hours on (date) No sedatives or narcotics administered except by order of anesthesiologist One ampule naloxone at bedside at all times Main IV access or heparin-lock at all times Measure and record respiratory rate q 1 h; for respiratory rate ⬍8/min, give naloxone, 0.2 mg IV slowly over 2 min; notify anesthesiologist Supplemental analgesia: Morphine 2 mg IV q 1-2 h PRN -orKetorolac 15 mg IV q 6 h PRN -orIbuprofen 400 mg PO q 6 h PRN For pruritus: nalbuphine, 5 mg IV q 4 h PRN itching For nausea/vomiting: ondansetron 4 mg IV q 6 h PRN nausea and vomiting For pain, pruritus, or nausea/vomiting unresponsive to above, page the anesthesiologist on call This protocol covers 24 h after each dose of neuraxial opioid
through a combination of intrathecal morphine and IV PCA supplementation.
Other Intrathecal Opioids Fentanyl Fentanyl can be used for analgesia at cesarean delivery and the maximal clinical benefit can be obtained with very low doses (5-10 g). The duration of effective analgesia after intrathecal bupivacaine increases from 71.8 minutes without fentanyl to 192 minutes with 6.25 g of fentanyl (Fig 11), but 24-hour supplemental narcotic usage is not affected.48 When added to intrathecal lidocaine anesthesia, fentanyl has similar effects, but the duration of analgesia is shorter.49 The short duration of effective analgesia even at high doses limits the value of intrathecal fentanyl as a postoperative analgesic. Pruritus occurs frequently, but rarely requires treatment, and fentanyl appears to actually decrease the incidence of nausea and vomiting intraoperatively.
Others Subarachnoid sufentanil, up to 10 g, has very similar analgesic properties to fentanyl. Like fentanyl, a short duration limits the
usefulness of sufentanil as a postoperative analgesic.50 Subarachnoid buprenorphine at a dose of 0.045 mg also prolongs the pain-free interval after bupivacaine spinal anesthesia, perhaps as long as 6 to 7 hours. Its only advantage over morphine would seem to be a lower incidence of pruritus.51 Other subarachnoid opioids that have been used in nonpregnant populations include methadone and oxymorphone. Methadone produces analgesia of shorter duration and less consistent quality than morphine, even at doses as high as 20 mg.52 Oxymorphone provides approximately 16 hours of analgesia when administered intrathecally, with predictable adverse effects of pruritus, nausea, and vomiting (Table 4).53 Nalbuphine has been combined with intrathecal morphine to attempt to decrease morphine’s adverse effects. It has no effect on the incidence or severity of pruritus or on postoperative analgesic use, but it tends to increase nausea.
Nonopioid Intrathecal Analgesics Epinephrine may prolong the anesthesia produced by intrathecal local anesthetics. However, the addition of epinephrine to 0.2 mg of intrathecal morphine does not increase the duration of postoperative analgesia or decrease supplemental analgesic requirements after cesarean delivery.54
Conclusion For spinal anesthesia for cesarean delivery, the combination of 0.1 mg of morphine and 10 g of fentanyl with either lidocaine
Fig 9. Mean 24-hour PCA morphine use after doses of intrathecal morphine from 0 to 0.5 mg in parturients after cesarean delivery. Data are mean (standard error). Adapted from Palmer et al.45
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Fig 10. Mean 24-hour pruritus scores in parturients after doses of intrathecal morphine from 0 to 0.5 mg. Adapted from Palmer et al.45 CRAIG M. PALMER
Fig 11. Duration of effective analgesia after intrathecal doses of fentanyl ranging from 0 to 50 g in parturients undergoing cesarean delivery with spinal (subarachnoid) anesthesia. Reprinted with permission from Palmer CM, D’Angelo R, Paech MJ: Handbook of Obstetric Anesthesia. Oxford: Bios Scientific Publishers, 2002. Adapted from Hunt et al.48
or bupivacaine is a good way to insure both intraoperative and postoperative analgesia. Morphine provides 18 to 24 hours of good to excellent postoperative analgesia for most parturients, but if a patient is having significant discomfort, then supplemental analgesia is appropriate. This could be IV PCA morphine, but many parturients are able to take oral analgesics within hours after their surgery, and these medications can be equally effective. Fentanyl may enhance intraoperative comfort and provide some early postoperative analgesia. Because of the very small volumes of opioids used with this technique, it is prudent to measure these drugs in tuberculin syringes to minimize the risk of accidental overdose. As with epidural morphine analgesia, careful postoperative monitoring of patients (respiratory rates) is essential.
Continuous Intrathecal Analgesia Continuous intrathecal analgesia can be used in those patients who have an intrathecal catheter in place. Such a technique allows medications to be titrated to patient comfort and additional boluses given for breakthrough pain. Generally speaking, the highly lipid-soluble opioids, with their fast onset and relatively short duration, are the best-suited agents. A combination of bupivacaine and fentanyl will provide adequate analgesia for most parturients after cesarean delivery (fentanyl 15 g/h with bupivacaine 1.5 mg/h). Sufentanil, 2.5 to 5 g/h, can also be used.55 These options are quite similar to intrathecal analgesics used for labor analgesia, either as infusions or as part of a combined spinal– epidural technique. Intrathecal sufentanil has been associated with significant respiratory depression in a number of patients;56,57 for this reason, closer monitoring, such as continuous pulse oximetry or an intensive care unit, should be used (Table 5).
PCA PCA can be very effective for postcesarean analgesia. Although epidural or intrathecal morphine analgesia is usually rated suPOSTCESAREAN ANALGESIA
perior (by patients) to the analgesia provided by PCA morphine, overall patient satisfaction with PCA is as high, probably because of the feeling of control that PCA provides parturients.58 Both PCA and neuraxial morphine are markedly more effective than intramuscular injections. The choice of opioid for use with PCA does not make any difference in patient satisfaction or adverse effects when equipotent doses are used. Likewise, use of a basal infusion does not change 24-hour opioid usage, but may decrease pain scores with movement. This minor advantage is offset by a higher incidence of nausea.59 Finally, PCA is an excellent choice to use in combination with neuraxial techniques for postcesarean analgesia, and it is an effective way to titrate postoperative analgesia to individual requirements. After initial IV titration of analgesics in the postanesthesia care unit, commonly used PCA regimens would include morphine, 1.5 to 2.0 mg IV q 10 minutes, or meperidine, 10 to 15 mg IV q 8 to 10 minutes. Dosage and time intervals can be adjusted based on individual response.
Epidural PCA Patient-controlled epidural analgesia (PCEA) allows the use of local anesthetics, opioids, and multiple combinations for postoperative analgesia. Compared with single bolus epidural morphine, use of opioid-only PCEA with fentanyl or sufentanil provides comparable analgesia, but the high total doses of opioid used by parturients raise the question of whether the analgesic effects are mediated primarily by systemic uptake or by a true spinal mechanism. As with IV PCA, a basal infusion does not improve the quality of pain relief with PCEA. Background infusions do increase sedation.60 When meperidine is used for PCEA, parturients use ⬃50% less opioid via the PCEA route than the PCA route. Sedation scores are predictably higher with IV PCA (Fig 12).61 Local anesthetics are often added to PCEA for postcesarean analgesia. The concentration of local anesthetic must be low to avoid significant sensory or motor blockade, because many of these patients are ambulatory within hours of surgery. PCEA with fentanyl or buprenorphine plus 0.03% bupivacaine produces effective analgesia, but motor block interferes with ambulation.62 With a lower concentration of bupivacaine (0.01%), ambulation is not affected, but the dose of fentanyl consumed is comparable to that with plain fentanyl PCEA. Thus, it is unclear what benefit including dilute bupivacaine in a PCEA solution provides. Clonidine and epinephrine (which activate ␣-2 adrenergic receptors), and neostigmine (which prevents the breakdown of synaptically released acetylcholine) also have been used with PCEA.63,64 When combined with sufentanil PCEA, both epinephrine and clonidine significantly reduce epidural opioid use. Unfortunately, clonidine significantly decreases blood
TABLE 4. Summary of Intrathecal Opioid Options Opioid
Dose
Duration
Morphine Fentanyl Sufentanil Buprenorphine Methadone Oxymorphine
0.1-0.2 mg 5-10 g Up to 5 g Limited experience; doses and durations not well characterized; subarachnoid (spinal) use not recommended
18-24 h 3-4 h 3-4 h
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TABLE 5. Continuous Intrathecal Analgesia Medications
Initial Bolus
Infusion
Comments
Sufentanil Fentanyl/bupivacaine
5 g Fentanyl 25 g with bupivacaine 2.5 mg
2.5-5 g/h Fentanyl 15 g/h bupivacaine 1.5 mg/h
Mix as 1 g/mL infusion Mix infusion with fentanyl 5 g and bupivacaine 0.5 mg per mL run at 3 mL/h*
*To mix infusion: Begin with 50 mL of normal saline; withdraw 15 mL; add 5 mL of .5% bupivacaine and 5 mL of fentanyl. Note: Most commercial infusion bags are slightly overfilled, therefore these numbers are only approximations.
pressure and heart rate, and neostigmine, even at very low doses, significantly increases nausea and vomiting. These adverse effects have limited the clinical utility of both clonidine and neostigmine. Clearly, PCEA can be an effective technique for postcesarean analgesia. Whether it offers distinct advantages over epidural or intrathecal morphine is a matter of dispute. A disadvantage is the necessity to maintain a functioning epidural catheter in the postoperative period. Furthermore, in many practices cesarean delivery is more likely to be accomplished with spinal than with epidural anesthesia, which precludes the technique. It remains a useful technique for selected patients and populations.
Nonsteroidal Agents Nonsteroidal anti-inflammatory drugs (NSAIDs) may be of value in this population. As noted above, despite the good quality of analgesia available with neuraxial techniques, supplemental analgesia is sometimes necessary, and NSAIDs (both oral and parenteral) are useful adjuncts to epidural or intrathecal morphine. Also, if patients have oral intake restricted for some time after delivery, then a parenteral NSAID can be used as an alternative to oral medications for supplemental analgesia. NSAIDs lack the potency to provide complete analgesia after a cesarean delivery. Thirty mg of ketorolac is roughly comparable to 75 mg of meperidine (intramuscular dosing), but analgesia after ketorolac is inconsistent and of short duration.65 When administered via continuous IV infusion, diclofenac or ketoprofen decrease postoperative opioid requirements by about 40% when compared with placebo.66 Studies of NSAIDs as adjuncts to neuraxial morphine have shown inconsistent results. Although in some situations NSAIDs can decrease postoperative opioid use, at this point it is premature to make a blanket recommendation regarding their use.
Fig 12. A comparison of pain scores between IV PCA and PCEA with meperidine after cesarean delivery. The solid line represents the period parturients received PCEA and the dashed line represents the period they received IV PCA in this blinded, crossover study. Reprinted with permission from Palmer CM, D’Angelo R, Paech MJ: Handbook of Obstetric Anesthesia. Oxford: Bios Scientific Publishers, 2002. Adapted from Paech et al.61
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Conclusion Cesarean delivery is probably the most common major surgical procedure performed in the world today. This huge number of anesthetics being performed in a remarkably homogeneous population (all being female, relatively young, and usually healthy) has allowed analgesic options to be systematically evaluated. Given current understanding of analgesic dose-response relationships, planning a cesarean anesthetic should include planning for postoperative analgesia. The variety of available options means there is an effective technique for every patient.
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