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A variety of neuraxial (primarily epidural) and peripheral regional analgesic techniques may be employed for the effective treatment of postoperative pain (see Chapter 43 and Chapter 44 ). In general, epidural and peripheral techniques can provide superior analgesia (particularly when local anesthetics are used) compared with systemic opioids,[151] and use of these techniques may even reduce morbidity and mortality.[19] [23] However, there are risks associated with the use of these techniques, and the clinician should evaluate the risks and benefits of these techniques on an individual basis in determining the appropriateness of neuraxial or peripheral regional techniques for each patient, especially in light of some of the controversies about the use of these techniques in the presence of various anticoagulants.
Administration of a single dose of opioid may be efficacious as a sole or adjuvant analgesic agent when administered intrathecally or epidurally. One of the most important factors in determining the clinical pharmacology for a particular opioid is its degree of lipophilicity (versus hydrophilicity) ( Table 72-4 ). Once inside the cerebrospinal fluid (CSF) through direct intrathecal injection or gradual migration from the epidural space, hydrophilic opioids (i.e., morphine and hydromorphone) tend to remain within the CSF and produce a delayed but longer duration of analgesia along with a generally higher incidence of side effects due to the cephalad spread of the hydrophilic opioid.[152] Neuraxial administration of lipophilic opioids, such as fentanyl and sufentanil, tends to provide rapid onset of analgesia, and the rapid clearance from the CSF may limit cephalad spread and development of certain side effects such as delayed respiratory depression.[152] [153] The site of analgesic action for hydrophilic opioids is overwhelmingly spinal, but the primary site of action (spinal versus systemic) for single-dose neuraxial lipophilic opioids is not as certain.[154] [155] [156]
The differences in pharmacokinetics between lipophilic and hydrophilic
opioids may influence the choice of opioid in an attempt to optimize analgesia and
minimize side effects for a particular clinical situation. Single-dose
| Properties | Lipophilic Opioids | Hydrophilic Opioids |
|---|---|---|
| Common agents | Fentanyl, sufentanil | Morphine, hydromorphone |
| Onset of analgesia | Rapid onset (5–10 min) | Delayed onset (30–60 min) |
| Duration of analgesia * | Shorter duration (2–4 hr) | Longer duration (6–24 hr) |
| CSF spread | Minimal CSF spread | Extensive CSF spread |
| Site of action | Spinal ± systemic | Primarily spinal |
| Side effects |
|
|
| Nausea and vomiting | Lower incidence with lipophilic versus hydrophilic opioids | |
| Pruritus | Lower incidence with lipophilic versus hydrophilic opioids | |
| Respiratory depression | Primarily early; minimal delayed | Both early (<6 hr) and delayed (>6 hr) possible |
| CSF, Cerebrospinal fluid. | ||
Single-dose epidural administration of lipophilic and hydrophilic opioids is used to provide postoperative analgesia, with considerations generally similar to those discussed with single-dose intrathecal administration of opioids. A single bolus of epidural fentanyl may be administered to provide rapid postoperative analgesia; however, diluting the epidural dose of fentanyl (typically 50 to 100 µg) in at least 10 mL of preservative-free normal saline is suggested to decrease the onset and prolong the duration of analgesia, possibly as a result of an increase in the initial spread and diffusion of the lipophilic opioid.[152] [160] Single-dose epidural morphine is effective for postoperative analgesia[161] and may decrease postoperative patient morbidity in selected patients.[162] [163] Use of a single-dose hydrophilic opioid may be especially helpful in providing postoperative epidural analgesia when the epidural catheter's location is not congruent with the surgical incision (e.g., lumbar epidural catheter for thoracic surgery). Lower doses of epidural morphine may be required for elderly patients and thoracic catheter sites.[152] [164] [165] Commonly used dosages for intrathecal and epidural administration of neuraxial opioids are provided in Table 72-5 .
| Drug | Intrathecal or Subarachnoid Single Dose * | Epidural Single Dose * | Epidural Continuous Infusion * |
|---|---|---|---|
| Fentanyl | 5–25 µg | 50–100 µg | 25–100 µg/hr |
| Sufentanil | 2–10 µg | 10–50 µg | 10–20 µg/hr |
| Alfentanil | — | 0.5–1 mg | 0.2 mg/hr |
| Morphine | 0.1–0.3 mg | 1–5 mg | 0.1–1 mg/hr |
| Diamorphine | 1–2 mg | 4–6 mg | — |
| Hydromorphone | — | 0.5–1 mg | 0.1–0.2 mg/hr |
| Meperidine | 10–30 mg | 20–60 mg | 10–60 mg/hr |
| Methadone | — | 4–8 mg | 0.3–0.5 mg/hr |
Analgesia delivered through an indwelling epidural catheter is a safe and effective method for management of acute postoperative pain[152] [166] (see Chapter 43 ). Postoperative epidural analgesia can provide superior analgesia compared with systemic opioids.[167] [168] [169] [170] [171] [172] However, it is important to realize that epidural analgesia is not a generic term but incorporates a wide range of options, including the choice and dose of analgesic agents, location of catheter placement, and onset and duration of perioperative use.[152] [166] Although this section focuses on the postoperative management of epidural analgesia, it is important to realize that intraoperative use of the epidural catheter as part of a combined epidural-general anesthetic technique results in less pain and accelerated patient recovery immediately after surgery compared with general anesthesia followed by systemic opioids.[173] Each of these options may affect the quality of postoperative analgesia, patient-oriented outcomes, and even rates of morbidity and mortality.
Epidural infusions of local anesthetic alone may be used for postoperative analgesia, but in general, they are not as effective in controlling pain as local anesthetic-opioid epidural analgesic combinations[166] [174] [175] (see Chapter 14 ). The precise location of the action of local anesthetics in the epidural space is not clear, and potential sites include the spinal nerve roots, dorsal root ganglion, or spinal cord itself.[156] Although some anatomic data suggest that the initial site of epidural local anesthetic block is at the nerve root sheath and dorsal root ganglion,[176] experimental data demonstrate that the initial site of action may not be at the spinal nerve root sleeve. [177] Epidural infusions of local anesthetic alone may be warranted for postoperative analgesia in an attempt to avoid opioid-related side effects; however, the sole use of local anesthetics is less common than use of a local anesthetic-opioid combination because of a significant failure rate (from regression of sensory block and inadequate analgesia) and relatively high incidence of motor block and hypotension.[166]
Opioids may be used alone for postoperative epidural infusions and do not generally cause motor block or hypotension from sympathetic blockade[166] (see Chapter 11 ). There are differences between continuous epidural infusions of lipophilic (e.g., fentanyl, sufentanil) and hydrophilic (e.g., morphine, hydromorphone) opioids. The analgesic site of action (spinal versus systemic) for continuous epidural infusions of lipophilic opioids is not clear, although several randomized clinical trials suggest that it is systemic[178] [179] [180] because there were no differences in plasma concentrations, side effects, or pain scores between those who received intravenous or epidural infusions of fentanyl.[178] [179] Although some data suggest a benefit from epidural (versus intravenous) infusions of lipophilic opioids,[181] the overall advantage of administering continuous epidural infusions of lipophilic opioids alone is marginal. [166]
The analgesic site of action for continuous hydrophilic opioid infusions is primarily spinal.[182] Continuous infusions of a hydrophilic opioid may be especially useful for providing postoperative analgesia when the site of catheter insertion is not congruent with the site of surgery or when side effects (e.g., hypotension, motor block) are attributed to the epidural local anesthetic. Use of a continuous infusion rather than intermittent bolus of epidural morphine may result in superior analgesia with fewer side effects.[182] [183] Continuous epidural infusions of hydrophilic opioids may provide superior analgesia compared with traditional PRN administration of systemic opioids.[184] [185]
Use of a local anesthetic and an opioid in an epidural infusion may have advantages over infusions using a local anesthetic or opioid alone. Compared with a local anesthetic or opioid alone, a local anesthetic-opioid combination provides superior postoperative analgesia (including improved dynamic pain relief), limits regression of sensory block, and possibly decreases the dose of local anesthetic administered, although the incidence of side effects may or may not be diminished. [52] [166] [174] [186] [187] [188] Continuous epidural infusion of a local anesthetic-opioid combination also provides superior analgesia compared with intravenous PCA with opioids.[40] [169] [171] [172] It is unclear whether the analgesic effect of the local anesthetic and opioid in the epidural analgesia is additive or synergistic. Experimental studies demonstrate a synergistic effect between local anesthetics and opioids[189] [190] [191] ; however, clinical trials suggest an additive effect.[174] [187] [188] [192]
The choice of local anesthetic for continuous epidural infusions varies. In general, bupivacaine, ropivacaine, or levobupivacaine is chosen because of the differential and preferential clinical sensory blockade with minimal impairment of motor function.[193] [194] [195] The concentrations used for postoperative epidural analgesia (≤0.125% bupivacaine or levobupivacaine or ≤0.2% ropivacaine) are lower than those used for intraoperative anesthesia. The choice of opioid also varies, although many clinicians choose to use a lipophilic opioid (fentanyl, 2 to 5 µg/mL, or sufentanil, 0.5 to 1 µg/mL) to allow for rapid titration of analgesia.[152] [166] [182] Use of a hydrophilic opioid (morphine, 0.05 to 0.1 mg/mL, or hydromorphone, 0.01 to 0.05 mg/mL) as part of a local anesthetic-opioid epidural analgesic regimen may also provide effective postoperative analgesia.[152] [182]
Although the optimal dose of local anesthetics and opioids that provides the lowest pain scores with the fewest medication-related side effects is unknown, a direct search method incorporating various epidural analgesic agents in patients undergoing major abdominal surgery revealed that the two optimal epidural bupivacaine-fentanyl combinations were 8 mg/hour of bupivacaine plus 30 µg/hour of fentanyl at a continuous infusion of 9 mL/hour or 13 mg/hour of bupivacaine plus 25 µg/hour of fentanyl at a continuous infusion of 9 mL/hour.[196] Further investigation is needed to determine the optimal combinations for other types of surgical procedures with different epidural catheter insertion sites and to compare the efficacy of these optimal continuous infusions with patient-controlled epidural analgesia (PCEA).
A variety of adjuvants may be added to epidural infusions to enhance
analgesia while minimizing side effects, but none has gained widespread acceptance.
Two of the more studied adjuvants are clonidine and epinephrine. Clonidine mediates
its analgesic effects primarily through the descending noradrenergic pathway, and
the epidural dose typically used ranges from 5 to 20 µg/hour.[196]
[197]
The clinical application of clonidine is
limited
by its side effects: hypotension, bradycardia, and sedation.[197]
Hypotension and bradycardia are both dose dependent. Epinephrine may improve epidural
analgesia, can increase sensory block, and is generally administered at a concentration
of 2 to 5 µg/mL.[198]
[199]
Epidural administration of NMDA antagonists, such as ketamine,
| Location of Incision | Examples of Surgical Procedures | Congruent Epidural Catheter Placement |
|---|---|---|
| Thoracic | Lung reduction, radical mastectomy, thoracotomy, thymectomy | T4-8 |
| Upper abdominal | Cholecystectomy, esophagectomy, gastrectomy, hepatic resection, Whipple | T6-8 |
| Middle abdominal | Cystoprostatectomy, nephrectomy | T7-10 |
| Lower abdominal | Abdominal aortic aneurysm repair, colectomy, radical prostatectomy, total abdominal hysterectomy | T8-11 |
| Lower extremity | Femoral-popliteal bypass, total-hip or total-knee replacement | L1-4 |
| L, lumbar level; T, thoracic level. | ||
Insertion of the epidural catheter congruent to the incisional dermatome (i.e., catheter-incision congruent analgesia) ( Table 72-6 ) results in optimal postoperative epidural analgesia by infusing analgesic agents to the appropriate incisional dermatomes, providing superior analgesia, minimizing side effects (e.g., lower extremity motor block and urinary retention), and decreasing morbidity.[23] [152] [166] Observational and randomized data suggest that compared with catheter-incision congruent epidural analgesia, catheter-incision incongruent epidural analgesia (e.g., lumbar catheter placement for abdominal or thoracic procedures) results in increased pain with early removal of epidural catheter because of ineffective analgesia.[201] [202] By targeting delivery of analgesic agents to the appropriate dermatomes, catheter-incision congruent epidural analgesia may result in lower drug requirements and decreased medication-related side effects. There is a higher incidence of lower extremity motor block with use of lumbar epidural catheters, which may also result in an earlier than anticipated termination of epidural analgesia.[201] [203] [204] Use of a high thoracic epidural does not inhibit sympathetic nerve activity in the lower extremities, which are supplied by sympathetic nerve fibers from T9 to L1.[205] Use of thoracic epidural analgesia for abdominal or thoracic surgery may result in a relatively low incidence of urinary retention and diminish the need for routine bladder catheterization.[206] The placement of thoracic epidural catheters appears to be relatively safe, and there is no evidence of a higher incidence of neurologic complications with placement of a thoracic (versus lumbar) epidural catheter.[207] [208] [209] The benefits of epidural analgesia in decreasing morbidity in patients undergoing abdominal and thoracic surgery are seen only with thoracic (congruent), not lumbar (incongruent), epidural catheter placement.[210] [211]
Many medication-related (opioid and local anesthetic) side effects can occur with use of postoperative epidural
Local anesthetics used in an epidural analgesic regimen may block sympathetic fibers and contribute to postoperative hypotension. Although the incidence of postoperative hypotension with postoperative epidural analgesia may be as high as approximately 7%, the average may be closer to 0.7% to 3%.[166] [212] [213] Strategies to treat noncritical hypotension due to epidural analgesia include decreasing the overall dose of local anesthetic administered (by decreasing the rate or concentration) or infusing an opioid epidural alone because it is unlikely that neuraxial opioid administration would contribute to postoperative hypotension.[152] [166]
Use of local anesthetics for postoperative epidural analgesia may also contribute to lower extremity motor block in approximately 2% to 3% of patients, [166] [212] and this may contribute to development of pressure sores in the heels.[214] A lower concentration of local anesthetics and catheter-incision congruent placement of epidural catheters for abdominal or thoracic procedures may decrease the incidence of motor block.[201] [215] Although motor block resolves in most cases after stopping the epidural infusion for approximately 2 hours, persistent or increasing motor block should be promptly evaluated, and spinal hematoma, spinal abscess, and intrathecal catheter migration should be considered as part of the differential diagnosis.[166]
Nausea and vomiting associated with neuraxial administration of a single dose opioid occurs in approximately 20% to 50% of patients,[216] [217] [218] and the cumulative incidence among those receiving continuous infusions of opioids may be as high as 45% to 80%.[219] [220] [221] Clinical and experimental data suggest that the incidence of neuraxial opioid-related nausea and vomiting is dose dependent. [222] [223] [224] [225] Nausea and vomiting from neuraxial opioids may be related to the cephalad migration of opioid within the CSF to the area postrema in the medulla.[216] Use of fentanyl alone or in combination with a local anesthetic in an epidural infusion is associated with a lower incidence of nausea and vomiting compared with infusions using morphine.[219] [220] [226] A variety of agents have been successfully used to treat neuraxial opioid-induced nausea and vomiting, including naloxone, droperidol, metoclopramide, dexamethasone, and transdermal scopolamine.[218] [221] [227] [228]
Pruritus is one of the most common side effects of epidural or intrathecal administration of opioids, with an incidence of approximately 60% compared with about 15% to 18% for epidural local anesthetic administration or systemic opioids. [81] [229] [230] Although the cause of neuraxial opioid-induced pruritus is uncertain, it does not appear to be associated with peripheral histamine release but may be related to central activation of an "itch center" in the medulla or opioid receptors in the trigeminal nucleus or nerve roots with cephalad migration of the opioid.[216] It is unclear whether the incidence of neuraxial opioid-related pruritus is dose dependent because a quantitative systematic review[229] suggests no evidence of a relationship, whereas other clinical and experimental studies indicate a significant correlation.[231] [232] [233] [234] Use of an epidural infusion of fentanyl alone or as part of a local anesthetic-opioid combination appears to be generally associated with a lower incidence of pruritus compared with morphine.[219] [226] [230] A variety of agents have been evaluated for the prevention and treatment of opioid-induced pruritus. Intravenous naloxone, naltrexone, nalbuphine, and droperidol appear to be efficacious for the pharmacologic control of opioid-induced pruritus.[229] Although pruritus is a common side effect, it is relatively easy to treat and is not considered an important clinical outcome to avoid.[235] The use of epidural morphine is associated with post-partum reactivation of herpes simplex labialis.[236]
Neuraxial opioids used in appropriate doses are not associated with a higher incidence of respiratory depression than that seen with systemic administration of opioids. The incidence of respiratory depression associated with neuraxial administration of opioids is dose dependent and typically ranges from 0.1% to 0.9%.[95] [213] [222] [237] [238] [239] The incidence of respiratory depression with continuous infusions of epidural opioids appears to be no greater than that seen after systemic opioid administration.[95] [239] Although some institutions require patients with continuous epidural infusions of hydrophilic opioids to receive monitoring in an intensive care unit setting, many large-scale trials have demonstrated the relative safety (incidence of respiratory depression < 0.9%) of this technique on regular surgical wards.[213] [238] [240] [241]
Neuraxial lipophilic opioids are considered to cause less delayed respiratory depression than hydrophilic opioids, although administration of lipophilic opioids may be associated with significant, early respiratory depression.[242] [243] [244] Delayed respiratory depression is primarily associated with hydrophilic opioids because of the cephalad spread of opioid, which typically occurs within 12 hours after injection. [239] Risks factors for respiratory depression with neuraxial opioids include increasing dose, increasing age, concomitant use of systemic opioids or sedatives, and possibly prolonged or extensive surgery, presence of comorbidities, and thoracic surgery.[239] Clinical assessments, such as respiratory rate, may not reliably predict a patient's ventilatory status or impending respiratory depression.[222] Treatment with naloxone (and airway management if necessary) is effective in 0.1- to 0.4-mg increments; however, the clinical duration of action is relatively short compared with the respiratory-depressant effect of neuraxial opioids, and a continuous infusion of naloxone (0.5 to 5 µg/kg/hour) may be needed.[152] [239]
Urinary retention associated with neuraxial administration of opioids is the result of an interaction with the opioid receptors in the spinal cord that decreases the detrusor muscle's strength of contraction.[216] The incidence of urinary retention seems to be higher
Epidural analgesia has been traditionally delivered as a fixed rate or continuous infusion (CEI); however, the administration of epidural analgesia through a patient-controlled device (PCEA) has become more common. Like intravenous PCA, PCEA allows for individualization of postoperative analgesic requirements and may have several advantages over CEI, including lower drug use,[249] [250] [251] greater patient satisfaction,[251] [252] and superior analgesia.[250] [253] PCEA may also provide superior analgesia and higher degrees of patient satisfaction compared with intravenous PCA.[167] [254]
PCEA is a safe and effective technique for postoperative analgesia
on routine surgical wards. Observational data
| Analgesic Solution * | Continuous Rate (mL/hr) | Demand Dose (mL) | Lockout Interval (min) |
|---|---|---|---|
| General Regimens |
|
|
|
| 0.05% bupivacine + 4 µg/mL fentanyl[212] | 4 | 2 | 10 |
| 0.0625% bupivacaine + 5 µg/mL fentanyl † | 4–6 | 3–4 | 10–15 |
| 0.1% bupivacaine + 5 µg/mL fentanyl[255] | 6 | 2 | 10–15 |
| 0.2% ropivacaine + 5 µg/mL fentanyl[203] | 5 | 2 | 20 |
| Thoracic Surgery |
|
|
|
| 0.0625–0.125% bupivacaine + 5 µg/mL fentanyl † | 3–4 | 2–3 | 10–15 |
| Abdominal Surgery |
|
|
|
| 0.0625% bupivacaine + 5 µg/mL fentanyl † | 4–6 | 3–4 | 10–15 |
| 0.125% bupivacaine + 0.5 µg/mL sufentanil[259] | 3–5 | 2–3 | 12 |
| 0.1–0.2% ropivacaine + 2 µg/mL fentanyl[215] [259] [260] [261] [262] [263] | 3–5 | 2–5 | 10–20 |
| Lower Extremity Surgery |
|
|
|
| 0.0625–0.125% bupivacaine + 5 µg/mL fentanyl † | 4–6 | 3–4 | 10–15 |
| 0.125% levobupivacaine + 4 µg/mL fentanyl[174] | 4 | 2 | 10 |
The optimal PCEA analgesic solution and delivery parameters are unclear. Use of a continuous or background infusion in addition to the demand dose is more common with PCEA than with intravenous PCA and may provide analgesia superior to the use of a demand dose alone.[257] [258] In general, most acute pain specialists are gravitating toward a variety of low-concentration local anesthetic-opioid combinations[259] [260] [261] [262] [263] ( Table 72-7 ) in an attempt to improve analgesia while minimizing side effects, such as motor block and respiratory depression. As for CEI, addition of an opioid to the local anesthetic can provide analgesia that is superior to either agent alone.[174] [187] [264] [265] A lipophilic opioid usually is chosen because the rapid analgesic effect and shorter duration of action may be more suitable for use with PCEA.[182] [212] The roles of other adjuvant agents (e.g., epinephrine, clonidine) have not been determined.
Use of perioperative epidural anesthesia and analgesia, especially with a local anesthetic-based analgesic solution, can attenuate the pathophysiologic response to surgery and may be associated with a reduction in mortality and morbidity compared with analgesia with systemic (opioid) agents.[19] [23] [51] [168] [266] A meta-analysis of randomized data (141 trials enrolling 9559 subjects) demonstrated that perioperative use of neuraxial anesthesia and analgesia (versus general anesthesia and systemic opioids) reduced overall mortality by approximately 30%.[266] Use of epidural analgesia can decrease the incidence of postoperative gastrointestinal, pulmonary, and possibly cardiac complications.[19] [23]
By inhibiting sympathetic outflow, decreasing the total opioid dose, and attenuating a spinal reflex inhibition of the gastrointestinal tract,[19] [267] postoperative thoracic epidural analgesia can facilitate return of gastrointestinal motility without contributing to anastomotic bowel dehiscence.[268] Randomized clinical trials demonstrate that use of postoperative thoracic epidural analgesia with a local anesthetic-based analgesic solution allows earlier return of gastrointestinal function and earlier fulfillment of discharge criteria.[167] [269] [270] Compared with those who receive epidural opioids for postoperative analgesia, patients who receive epidural local anesthetics have an earlier return of gastrointestinal motility after abdominal surgery.[269] [271] [272]
Perioperative use of epidural analgesia with a local anesthetic-based regimen in patients undergoing abdominal and thoracic surgery decreases postoperative pulmonary complications,[51] [168] presumably by preserving postoperative pulmonary function by providing superior analgesia and attenuating a spinal reflex inhibition of diaphragmatic function.[19] A meta-analysis of 48 randomized clinical trials[51] and another large, randomized clinical trial[168] demonstrated that use of thoracic epidural analgesia with a local anesthetic-based regimen decreased the incidence of pulmonary infections and complications. However, patients who receive postoperative epidural opioids, intercostal blocks, wound infiltration, or intrapleural analgesia do not have a significant decrease in the incidence of pulmonary complications.[51]
Use of postoperative thoracic, but not lumbar, epidural analgesia may decrease the incidence of postoperative myocardial infarction,[211] possibly by attenuating the stress response and hypercoagulability, improving postoperative analgesia, and providing a favorable redistribution of coronary blood flow.[22] [273] [274] The finding that only thoracic epidural analgesia decreases the incidence of postoperative myocardial infarction corroborates experimental data on the physiologic benefits of thoracic epidural analgesia, such as a reduction in the severity of myocardial ischemia or size of infarction, attenuation of sympathetically mediated coronary vasoconstriction, and improvement of coronary flow to areas at risk for ischemia. [275] [276] [277]
Although postoperative epidural analgesia appears to decrease postoperative gastrointestinal, pulmonary, and possibly cardiac morbidity, the benefits of postoperative epidural analgesia are not as clear for other areas such as postoperative coagulation, cognitive dysfunction,[278] [279] and immune function.[280] Despite the fact that many randomized clinical trials and meta-analyses show that use of intraoperative regional anesthesia decreases the incidence of hypercoagulable-related events (e.g., deep venous thrombosis, pulmonary embolism, vascular graft failure),[266] [281] [282] [283] [284] evidence of a beneficial effect of postoperative epidural analgesia in decreasing the incidence of hypercoagulable-related events is not compelling.[285] The effect of regional anesthesia and analgesia on these outcomes is equivocal at best, despite some physiologic evidence suggesting that epidural analgesia may attenuate adverse physiologic responses that may contribute to the development of these complications.
The benefits of postoperative epidural analgesia are optimized when the epidural catheter is inserted in a location corresponding to the dermatomes covered by the surgical incision (i.e., catheter-incision congruent analgesia), resulting in a lower dose of drug administered and decreased incidence of drug-induced side effects, such as pruritus, nausea, vomiting, urinary retention, motor block, and hypotension.[205] [212] [286] [287] [288] Compared with catheter-incision incongruent epidural analgesia, catheter-incision congruent analgesia[288] provides an earlier return of gastrointestinal function,[210] a lower incidence of myocardial infarction,[211] and superior analgesia. [201] [202] The ability for postoperative epidural analgesia to attenuate postoperative pathophysiology and improve outcomes also depends on the type of drugs used (opioids versus local anesthetics). Maximal attenuation of perioperative pathophysiology occurs with use of a local anesthetic-based epidural analgesic solution. The use of a local anesthetic-based (versus opioid-based) analgesic solution is associated with an earlier recovery of gastrointestinal motility after abdominal surgery[269] [271] [272] and less frequent occurrence of pulmonary complications.[51] Epidural analgesia is not a generic entity because different catheter locations and analgesic regimens may differentially affect perioperative morbidity.
Use of postoperative epidural analgesia is associated with an improvement in postoperative analgesia and other nontraditional outcomes such as patient satisfaction[94] and health-related quality of life (HRQL).[40] Compared with systemic opioids, epidural local anesthetics consistently provide superior analgesia.[51] [52] [167] [168] [169] [170] [171] [172] The data on the analgesic superiority of postoperative epidural analgesia reflect those seen with epidural analgesia during labor.[289] Although the concept of satisfaction is complex and difficult to measure accurately,[93] the analgesic benefits of postoperative epidural analgesia may contribute to greater patient satisfaction [94] and improve HRQL.[40]
The benefits of perioperative epidural anesthesia-analgesia must be weighed against the risks of this technique. Risks and benefits should be evaluated for each patient. There are complications associated with placement of an epidural catheter (see Chapter 43 ), with several risks associated with indwelling epidural catheters (i.e., epidural hematoma and abscess) that should be discussed in the context of postoperative epidural analgesia. Elements of routine monitoring for patients receiving neuraxial analgesia are supplied in Table 72-1 .
The concurrent use of anticoagulants and of neuraxial anesthesia and analgesia has always been a relatively
Different types and classes of anticoagulants have different pharmacokinetic properties that affect the timing of neuraxial catheter or needle insertion and catheter removal.[297] [298] Despite a number of observational and retrospective studies investigating the incidence of spinal hematoma in the setting of various anticoagulants and neuraxial techniques, there is no definitive conclusion regarding the absolute safety of neuraxial anesthesia and anticoagulation. The American Society of Regional Anesthesia and Pain Medicine (ASRA) lists a series of consensus statements based on the available literature for administration (insertion and removal) of neuraxial techniques in the presence of various anticoagulants, including oral anticoagulants (warfarin),[299] antiplatelet agents,[300] fibrinolytics-thrombolytics, [301] standard unfractionated heparin,[302] and low-molecular-weight heparin.[296] The ASRA consensus statements include the concepts that the timing of neuraxial needle or catheter insertion or removal should reflect the pharmacokinetic properties of the specific anticoagulant, that frequent neurologic monitoring is essential, that concurrent use of multiple anticoagulants may increase the risk of bleeding, and that the analgesic regimen should be tailored to facilitate neurologic monitoring, which may be continued in some cases for 24 hours after epidural catheter removal. An updated version of the ASRA consensus statements on neuraxial anesthesia and anticoagulation[303] can be found on their web site (www.asra.com), and some of these statements address the newer anticoagulants.
Infection associated with postoperative epidural analgesia may result from exogenous or endogenous sources.[166] Serious infections (e.g., meningitis, spinal abscess) associated with epidural analgesic are rare (<1 in 10,000),[304] [305] [306] although some researchers report a higher incidence (approximately 1 in 1000 to 2000).[241] [307] Closer examination of the studies that reported a higher incidence of epidural abscesses reveals that the patients had a relatively longer duration of epidural analgesia or presence of coexisting immunocompromising or complicating diseases (e.g., malignancy, trauma).[166] [241] [307] Use of epidural analgesia in the general surgical population with a typical duration of postoperative catheterization (approximately 2 to 4 days) is generally not associated with epidural abscess formation.[175] [212] [255] [256] A larger trial of postoperative epidural analgesia (mean catheterization of 6.3 days) in more than 4000 surgical cancer patients did not reveal any abscesses.[213] Even though serious infectious complications appear to be rare after short-term (<4 days) epidural infusions, there may be a relatively higher incidence of superficial inflammation or cellulitis (4% to 14%) and even higher rate of catheter colonization (20% to 35%), with the proportion of positive cultures increasing with the duration of catheterization.[308] [309] [310] Catheter colonization rate may not be a good predictor of epidural space infection.[310]
Although epidural analgesia may provide superior postoperative analgesia, epidural catheter migration out of the epidural space and into the intrathecal, intravascular, or subcutaneous space decreases the effectiveness of this technique. The failure rate (i.e., earlier than anticipated discontinuation of the catheter for any reason) ranges from approximately 6% to 25%, with many centers reporting a rate between 10% and 20%, but the incidence of actual premature epidural catheter dislodgment may be lower (mean, 5.7%; 95% CI: 4.0%–7.4%).[151] [175] [204] [212] [213] [255] [256] Fortunately, the rate of intrathecal (approximately 0.15%[96] [238] ) and intravascular (0.07% to 0.18%[238] [311] ) migration of an epidural catheter is much lower than the failure rate. Despite the less frequent occurrence of intravascular and intrathecal migration of postoperative epidural catheters, use of an epinephrine-containing test dose, administration of local anesthetic in fractionated doses, and aspiration of the catheter before bolus administration of local anesthetic may prevent complications (e.g., high or total spinal, seizures, neurotoxicity) associated with accidental administration of local anesthetics into the intravascular or intrathecal space. [166] The issue of whether lower extremity compartment syndrome can be consistently masked by use of a local anesthetic-based epidural analgesic regimen is unresolved because use of systemic opioid analgesia has also been associated with a delayed diagnosis of compartment syndrome.[312] [313] [314]
The use of peripheral regional analgesic techniques as a single injection or continuous infusion can provide superior analgesia compared with systemic opioids[315] [316] [317] [318] [319] [320] and may even result in improvement in various outcomes.[38] [94] [321] [322] A variety of wound infiltration and peripheral regional techniques (i.e., brachial plexus, lumbar plexus, femoral, sciatic-popliteal, and scalp nerve blocks) can be used to enhance postoperative analgesia. Peripheral regional techniques may have several advantages over systemic opioids (i.e., superior analgesia and decrease in opioid-related side effects) and neuraxial techniques (i.e., decreased risk of spinal hematoma). [323] The technical aspects of performing these blocks are described in Chapter 44 and several comprehensive review articles.[322] [323] [324] [325]
A one-time injection of local anesthetic for peripheral regional techniques may be used primarily for intraoperative anesthesia or as an adjunct for postoperative analgesia. Compared with placebo, peripheral nerve blocks with local anesthetics provide superior analgesia and are associated with decreased opioid use, decreased opioid-related side
Continuous infusions of local anesthetics can be administered through peripheral nerve catheters. Compared with systemic opioids, use of continuous infusions or patient-controlled peripheral analgesia results in superior analgesia, decreased opioid-related side effects, and greater patient satisfaction.[94] [320] [328] [329] Although some data are available,[330] [331] [332] the optimal parameters (i.e., local anesthetic, concentration, opioid, adjuvants, and continuous versus PCA versus intermittent boluses) for peripheral analgesia have not been determined. A combination of a continuous peripheral regional analgesic technique and systemic adjuvants, such as acetaminophen and ketorolac, may be used to provide an opioid-free postoperative analgesic regimen. [333]
Several nonepidural regional analgesic techniques can be used for management of postoperative thoracic pain, including paravertebral and intercostal blocks, interpleural (intrapleural) analgesia, and cryoanalgesia. The most promising technique appears to be the thoracic paravertebral block, which has been used for thoracic, breast, and upper abdominal surgery and for treatment of rib fracture pain. [334] [335] The possible sites of analgesia for the thoracic paravertebral block include direct somatic nerve, sympathetic nerve, and epidural blockade.[335] The thoracic paravertebral block can be administered as a single injection or continuous infusion through a catheter, may provide equal or superior analgesia compared with thoracic epidural analgesia, and is a valuable alternative to thoracic epidural analgesia. [336] [337] [338]
The analgesic efficacy of interpleural analgesia is controversial, as is its mechanism of action (i.e., sensory or sympathetic block, or both).[339] [340] Interpleural analgesia appears to be inferior to epidural and paravertebral analgesia for postoperative pain control, preservation of lung function after thoracotomy, and reduction of postoperative pulmonary complications. [51] [340] [341] [342] Intercostal blocks may provide short-term postoperative analgesia and may be repeated postoperatively; however, the incidence of pneumothorax increases with each intercostal nerve blocked (1.4% per nerve, with an overall incidence of 8.7% per patient).[343] Like interpleural analgesia, intercostal blocks do not reduce the incidence of pulmonary complications postoperatively compared with epidural analgesia.[51] Cryoanalgesia can be used for postoperative analgesia after thoracotomy but, like interpleural analgesia and intercostal blocks, does not appear to provide any analgesic advantage over epidural analgesia and is not effective for other types of postoperative pain.[344] [345] [346]
Local peripheral administration of opioids (e.g., intra-articular injection after knee surgery) may provide analgesia for up to 24 hours after surgery [347] [348] [349] and decrease the incidence of chronic pain[350] (see Chapter 61 ). Peripheral opioid receptors are found on the peripheral terminals of primary afferent nerves and are upregulated during inflammation of peripheral tissues.[58] The results of the several randomized clinical trials investigating this topic are summarized in three systematic reviews.[347] [348] [351] Use of a higher dose of intra-articular morphine (5 mg versus 1 mg) results in superior analgesia; however, there may be no advantage in the degree of analgesia provided between intra-articular and systemic opioids. [347] A systemic effect of intra-articularly injected morphine cannot be excluded.[348] Intra-articular injection of local anesthetics may provide a limited duration of postoperative analgesia, but the clinical benefit from intra-articular local anesthetics injections is unclear. [352]
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