Preventive Analgesia

Preventive analgesia is a method of preventing or attenuating the central sensitization that results from a painful insult and the inflammatory reaction that develops after the insult. Previously, the term “preemptive analgesia” described mainly the timing of pain intervention (i.e., before vs. after the insult). Its use was controversial, and proving its clinical relevance in clinical trials was difficult. Recent clinical trials have shown that the effectiveness and duration of pain treatment interventions are clinically relevant in blocking or attenuating the noxious stimuli and decreasing central sensitization to pain. For preventive analgesia to effectively prevent central sensitization and reduce postoperative and chronic pain, intensive multimodal analgesic interventions should be used during the perioperative period. Maximum benefit occurs when pain interventions are extended into the postoperative phase. The focus of this chapter is on available pain treatment intervention techniques and drugs for multimodal analgesia in the setting of surgery and trauma.

Multimodal Analgesia

Multimodal analgesia involves the administration of two or more analgesic agents by one or more routes that exert their effects via different analgesic mechanisms and ideally act synergistically at different sites in the nervous system, thereby providing superior analgesia with fewer side effects. The concept of a multimodal strategy, including regional analgesia, was introduced more than a decade ago to allow early ambulation, promote better rehabilitation, accelerate recovery, and reduce the length of hospital stay. In the ambulatory surgery setting, evidence has shown great promise for the use of local anesthetics, acetaminophen, and nonsteroidal anti-inflammatory drugs (NSAIDs), among other treatment options, with opioids being reserved as a rescue drug only. Some recent publications have found that NSAIDs and selective cyclooxygenase-2 (COX-2) inhibitors consistently reduce postoperative opioid requirements. Furthermore, the combination of several nonopioid analgesics with opioids delivered by patient-controlled analgesia (PCA) offers advantages over opioids alone. Multimodal pain control strategies for certain procedures could become an integral part of clinical pathways to provide effective postoperative analgesia and rehabilitation.

Pain Management Options

Pain management is an art; a clinician must balance the risks and benefits of each modality to customize treatment based on a patient’s specific needs. Many institutions have recognized that suboptimal treatment of acute postoperative pain occurs frequently and have begun to support the development of postoperative pain services, many of which are led by anesthesiologists who have clinical experience in regional anesthesia and knowledge of drug pharmacology to provide surgical patients with an optimal pain treatment plan that minimizes side effects. Even though pain treatment modalities may decrease morbidity, more common outcomes generally include improvement in the quality of recovery and quality of life. Patient satisfaction can be used as an indicator of an effective treatment response to these programs. Options available for the management of postoperative pain include, but are not limited to, various combinations of systemic and neuraxial opioids, nonopioid analgesics, and regional analgesia (neuraxial and perineural).

Opioids

Opium and its derivatives are the most commonly used medications for the treatment of acute and chronic pain ( Table 18.1 ). Opioids exert their analgesic effect through µ-opioid receptors. These receptors are located mainly in the central nervous system (CNS), although some are also present in the peripheral nervous system. The therapeutic benefits (and side effects) of morphine, the prototypical opioid analgesic agent, are mediated predominantly through activation of µ-opioid receptors and less likely through the δ- and κ-receptor subtypes. Although opioids do not exhibit an analgesic ceiling effect, the analgesic efficacy of opioids can be limited by the development of adverse effects such as nausea, vomiting, pruritus, ileus, and respiratory depression.

One of the many advantages of opioid analgesics for the treatment of acute postoperative pain is that it can be administered via a number of routes (e.g., subcutaneous, oral, intravenous [IV], intramuscular [IM], intranasal, transmucosal, and neuraxial). This feature enhances the versatility of opioids as a therapeutic agent. For the treatment of moderate to severe postoperative pain, opioids are typically administered parenterally (IV, IM), although there may be wide individual variability in the relationship between opioid dose, serum concentration, and analgesic response in the treatment of postoperative pain. IV administration of opioids is desirable for treating acute postoperative pain because of the rapid and reliable onset of analgesia. Oral administration of opioids is the most common form used for the treatment of mild to moderate postoperative pain or when inpatients have successfully initiated oral intake.

Opioid receptor physiology is complex and regulated by multiple mechanisms that may play a role in the development of opioid receptor tolerance and desensitization. Tolerance and desensitization may contribute not only to a short-term decrease in analgesic efficacy but also to long-term changes in receptor sensitivity. Desensitization may lead to increased analgesic requirements for a similar pain response.

IV PCA is considered the “gold standard” by which systemic opioids are delivered postoperatively. Unlike traditional “as needed” (PRN) analgesic regimens, IV PCA allows the clinician to compensate for several factors, including the wide interpatient and intrapatient variability in analgesic needs, variability in serum drug levels, and administrative delays, which might result in inadequate postoperative analgesia. The IV PCA device per se has a safety mechanism integrated into its design, although when the negative feedback loop is violated, excessive sedation or respiratory depression may occur. Most of the problems related to the use of IV PCA are caused by user or operator error and are not attributable to the device itself.

Variables that can be programmed into an IV PCA device include the demand or bolus dose, lockout interval, and background infusion. Optimal settings for IV PCA administration of opioids for the management of postoperative pain are not known; however, there are general principles that may promote effective postoperative analgesia. The setting for the demand or bolus dose should be sufficient to provide analgesia after multiple self-administered doses; it should not be an excessive dose that may result in adverse effects such as respiratory depression. For opioid-naïve patients, a commonly used demand dose for morphine is 0.5 to 2.5 mg, for fentanyl it is 10 to 20 µg, and for hydromorphone it is 0.05 to 0.25 mg ( Table 18.2 ). Commonly used lockout intervals range from 5 to 10 minutes, and varying the interval within this range appears to have no effect on analgesia or side effects. The final variable is the continuous or background infusion. Although use of a background infusion was initially thought to provide improved analgesia, especially during sleep, routine use of continuous or background infusions in IV PCA in adult opioid-naïve patients is not recommended because it increases the incidence of adverse effects such as respiratory depression. Use of a background infusion in opioid-naïve patients, even if limited to nighttime, does not improve analgesia or sleep patterns. However, a background infusion for opioid-tolerant or pediatric patients may be appropriate.

When compared with traditional PRN analgesic regimens, use of IV PCA may be associated with improved patient outcomes, including superior postoperative analgesia, improved patient satisfaction, and possibly decreased risk for pulmonary complications. At least two meta-analyses have been conducted to compare IV PCA with PRN administration of opioids. Both meta-analyses demonstrated that the analgesia provided by IV PCA is superior to that achieved with PRN administration. An early meta-analysis of 15 randomized trials in which PRN IM dosing was compared with IV PCA failed to demonstrate a reduction in opioid consumption. IV PCA had no obvious economic benefit, although it may be associated with fewer pulmonary complications. In addition, patients tended to prefer IV PCA, which may result in greater patient satisfaction. Although IV PCA provides no apparent decrease in cost or length of hospital stay, it does reduce demand on the nursing staff, who are required for delivery of IV or IM PRN analgesics. This reduced administration by the nursing staff may indeed have a cost benefit. The incidence of opioid-related side effects, including respiratory depression (0.5%), from IV PCA does not appear to differ significantly from that of other administration routes (e.g., IV, IM, or subcutaneous). Many factors could contribute to the occurrence of respiratory depression with IV PCA, including the use of a background infusion, concomitant use of a sedative or hypnotic agent, advanced age, and the presence of pulmonary disease or sleep apnea.

Transdermal delivery of fentanyl, a continuous passive dose, is not indicated for the treatment of acute pain but could be an option for the treatment of chronic cancer pain; it could also be an alternative to oral opioids when patients cannot tolerate oral intake for an extended time. A recent technological development has added the process of iontophoresis to substantially increase dermal penetration capacity and thereby allow in essence a “PCA fentanyl patch.” Clinical studies have shown iontophoretic patient-controlled transdermal fentanyl to be superior to placebo and comparable to IV PCA with morphine for the treatment of acute postoperative pain.

Morphine, in either extended-release or immediate-release form, is still the gold standard for oral opioids. Oxycodone is commonly used alone or in combination with an adjuvant such as acetaminophen. One should be cautious of exceeding the total recommended daily dose of acetaminophen because of hepatic toxicity. Transmucosal fentanyl could be used when acute intense pain is anticipated. With opioid conversion, especially in opioid-tolerant patients, the dose should be decreased by 33% because of incomplete cross-tolerance between drugs.

Tramadol is a centrally acting, synthetic analgesic agent that is structurally related to codeine and morphine. The use of tramadol for postoperative analgesia may confer several advantages over traditional opioids, including the relative lack of respiratory depression, major organ toxicity, constipation, and dependence. Common side effects of tramadol include dizziness, drowsiness, sweating, nausea, vomiting, dry mouth, and headache.

Conversion from one opioid or one route of administration to another should de done with caution to avoid underdosing or overdosing. A conversion table ( Table 18.3 ) may facilitate equianalgesic conversion; however, it provides only an estimate to assist in initiating the opioid dose.

Nonopioid Analgesics

Opioids

Opium and its derivatives are the most commonly used medications for the treatment of acute and chronic pain ( Table 18.1 ). Opioids exert their analgesic effect through µ-opioid receptors. These receptors are located mainly in the central nervous system (CNS), although some are also present in the peripheral nervous system. The therapeutic benefits (and side effects) of morphine, the prototypical opioid analgesic agent, are mediated predominantly through activation of µ-opioid receptors and less likely through the δ- and κ-receptor subtypes. Although opioids do not exhibit an analgesic ceiling effect, the analgesic efficacy of opioids can be limited by the development of adverse effects such as nausea, vomiting, pruritus, ileus, and respiratory depression.

One of the many advantages of opioid analgesics for the treatment of acute postoperative pain is that it can be administered via a number of routes (e.g., subcutaneous, oral, intravenous [IV], intramuscular [IM], intranasal, transmucosal, and neuraxial). This feature enhances the versatility of opioids as a therapeutic agent. For the treatment of moderate to severe postoperative pain, opioids are typically administered parenterally (IV, IM), although there may be wide individual variability in the relationship between opioid dose, serum concentration, and analgesic response in the treatment of postoperative pain. IV administration of opioids is desirable for treating acute postoperative pain because of the rapid and reliable onset of analgesia. Oral administration of opioids is the most common form used for the treatment of mild to moderate postoperative pain or when inpatients have successfully initiated oral intake.

Opioid receptor physiology is complex and regulated by multiple mechanisms that may play a role in the development of opioid receptor tolerance and desensitization. Tolerance and desensitization may contribute not only to a short-term decrease in analgesic efficacy but also to long-term changes in receptor sensitivity. Desensitization may lead to increased analgesic requirements for a similar pain response.

IV PCA is considered the “gold standard” by which systemic opioids are delivered postoperatively. Unlike traditional “as needed” (PRN) analgesic regimens, IV PCA allows the clinician to compensate for several factors, including the wide interpatient and intrapatient variability in analgesic needs, variability in serum drug levels, and administrative delays, which might result in inadequate postoperative analgesia. The IV PCA device per se has a safety mechanism integrated into its design, although when the negative feedback loop is violated, excessive sedation or respiratory depression may occur. Most of the problems related to the use of IV PCA are caused by user or operator error and are not attributable to the device itself.

Variables that can be programmed into an IV PCA device include the demand or bolus dose, lockout interval, and background infusion. Optimal settings for IV PCA administration of opioids for the management of postoperative pain are not known; however, there are general principles that may promote effective postoperative analgesia. The setting for the demand or bolus dose should be sufficient to provide analgesia after multiple self-administered doses; it should not be an excessive dose that may result in adverse effects such as respiratory depression. For opioid-naïve patients, a commonly used demand dose for morphine is 0.5 to 2.5 mg, for fentanyl it is 10 to 20 µg, and for hydromorphone it is 0.05 to 0.25 mg ( Table 18.2 ). Commonly used lockout intervals range from 5 to 10 minutes, and varying the interval within this range appears to have no effect on analgesia or side effects. The final variable is the continuous or background infusion. Although use of a background infusion was initially thought to provide improved analgesia, especially during sleep, routine use of continuous or background infusions in IV PCA in adult opioid-naïve patients is not recommended because it increases the incidence of adverse effects such as respiratory depression. Use of a background infusion in opioid-naïve patients, even if limited to nighttime, does not improve analgesia or sleep patterns. However, a background infusion for opioid-tolerant or pediatric patients may be appropriate.

When compared with traditional PRN analgesic regimens, use of IV PCA may be associated with improved patient outcomes, including superior postoperative analgesia, improved patient satisfaction, and possibly decreased risk for pulmonary complications. At least two meta-analyses have been conducted to compare IV PCA with PRN administration of opioids. Both meta-analyses demonstrated that the analgesia provided by IV PCA is superior to that achieved with PRN administration. An early meta-analysis of 15 randomized trials in which PRN IM dosing was compared with IV PCA failed to demonstrate a reduction in opioid consumption. IV PCA had no obvious economic benefit, although it may be associated with fewer pulmonary complications. In addition, patients tended to prefer IV PCA, which may result in greater patient satisfaction. Although IV PCA provides no apparent decrease in cost or length of hospital stay, it does reduce demand on the nursing staff, who are required for delivery of IV or IM PRN analgesics. This reduced administration by the nursing staff may indeed have a cost benefit. The incidence of opioid-related side effects, including respiratory depression (0.5%), from IV PCA does not appear to differ significantly from that of other administration routes (e.g., IV, IM, or subcutaneous). Many factors could contribute to the occurrence of respiratory depression with IV PCA, including the use of a background infusion, concomitant use of a sedative or hypnotic agent, advanced age, and the presence of pulmonary disease or sleep apnea.

Transdermal delivery of fentanyl, a continuous passive dose, is not indicated for the treatment of acute pain but could be an option for the treatment of chronic cancer pain; it could also be an alternative to oral opioids when patients cannot tolerate oral intake for an extended time. A recent technological development has added the process of iontophoresis to substantially increase dermal penetration capacity and thereby allow in essence a “PCA fentanyl patch.” Clinical studies have shown iontophoretic patient-controlled transdermal fentanyl to be superior to placebo and comparable to IV PCA with morphine for the treatment of acute postoperative pain.

Morphine, in either extended-release or immediate-release form, is still the gold standard for oral opioids. Oxycodone is commonly used alone or in combination with an adjuvant such as acetaminophen. One should be cautious of exceeding the total recommended daily dose of acetaminophen because of hepatic toxicity. Transmucosal fentanyl could be used when acute intense pain is anticipated. With opioid conversion, especially in opioid-tolerant patients, the dose should be decreased by 33% because of incomplete cross-tolerance between drugs.

Tramadol is a centrally acting, synthetic analgesic agent that is structurally related to codeine and morphine. The use of tramadol for postoperative analgesia may confer several advantages over traditional opioids, including the relative lack of respiratory depression, major organ toxicity, constipation, and dependence. Common side effects of tramadol include dizziness, drowsiness, sweating, nausea, vomiting, dry mouth, and headache.

Conversion from one opioid or one route of administration to another should de done with caution to avoid underdosing or overdosing. A conversion table ( Table 18.3 ) may facilitate equianalgesic conversion; however, it provides only an estimate to assist in initiating the opioid dose.

Nonopioid Analgesics

Continuous Epidural Analgesia

Continuous epidural analgesia may provide a longer duration of analgesia than an individual injection and analgesia superior to that with systemic opioids. Postoperative use of continuous epidural analgesia may be associated with improved patient morbidity by decreasing pulmonary ( Fig. 18.1 ), cardiovascular, and gastrointestinal ( Fig. 18.2 ) complications in high-risk patients and after high-risk procedures. However, many factors can affect the overall outcomes of continuous epidural analgesia. Among them are the congruency of epidural catheter location and the surgical incision, the type of analgesic regimen, and whether the epidural is used as part of a multimodal approach. Local anesthetics used alone or in combination with opioids will offer better physiologic benefit to the patient than opioid use alone. However, premature discontinuation of epidural analgesia may negate its physiologic benefit. When compared with systemic administration of opioids, local anesthetic–based epidural regimens provide superior analgesia and may decrease opioid-related side effects; epidural infusion of opioids alone may be used to avoid hypotension when sympathetic blockade is a concern.

Epidural local analgesia versus systemic opioids: pulmonary complications. CI, confidence interval; RR, relative risk.

(Redrawn from Ballantyne JC, Carr DB, deFerranti S, et al. The comparative effects of postoperative analgesic therapies on pulmonary outcome: cumulative meta-analyses of randomized, controlled trials. Anesth Analg . 1998;86:598-612.)

Epidural local analgesis versus opioids in patients with myocardial infarction. LEA, lumbar epidural analgesia; OR, odds ratio; TEA, thoracic epidural analgesia.

(Redawn from Beattie WS, Badner NH, Choi P. Epidural analgesia reduces postoperative myocardial infarction: a meta-analysis. Anesth Analg . 2001;93:853-858.)

Postoperative epidural analgesia may be delivered as a fixed continuous infusion or as patient-controlled epidural analgesia (PCEA). Based on the principles of PCA, PCEA allows individualization of postoperative analgesic requirements, reduces drug use, improves patient satisfaction, and provides superior analgesia.

The choice of drug for epidural analgesia is usually a local anesthetic with a long duration of action. It should exhibit preferential clinical sensory blockade and cause only minimal impairment of motor function. Another option is a lipophilic opioid (e.g., fentanyl or sufentanil), which allows relatively rapid titration of analgesia, although hydrophilic opioids (e.g., morphine and hydromorphone) may also be used for postoperative analgesia.

Even though clonidine and epinephrine are potentially useful adjuvants, neither is widely used clinically. Clonidine may enhance postoperative analgesia by activating the descending noradrenergic pathway; however, its clinical usefulness is typically limited by the presence of hypotension, bradycardia, and sedation. Epinephrine has been shown to improve epidural analgesia and increase sensory block in the postoperative setting.

Neuraxial Opioids

Classification of opioids is based on their lipophilic property. Hydrophilic opioids (e.g., morphine and hydromorphone) tend to remain within cerebrospinal fluid (CSF) after neuraxial administration and usually produce a delayed but longer duration of analgesia. They also tend to cause a higher incidence of side effects because of CSF spread, unlike lipophilic opioids (e.g., fentanyl and sufentanil), which tend to provide a faster onset but shorter duration of analgesia as a result of rapid clearance from CSF. Hydrophilic opioids provide analgesia primarily via a spinal mechanism, whereas lipophilic opioids provide analgesia via either a spinal or systemic mechanism. Single-shot neuraxial administration of a lipophilic opioid may be appropriate for short-duration analgesia, but single-shot neuraxial administration of a hydrophilic opioid will be appropriate for longer-duration analgesia. The latter may provide effective postoperative analgesia in an appropriately monitored setting ( Table 18.4 ). It is essential that the dose of neuraxial opioid be reduced with use in older patients.

Although some studies indicate that the incidence of pulmonary and cardiovascular comorbidity may be lower with neuraxial morphine than with systemic opioids, the overall benefit is observed only when compared with intermittent IV doses and not when compared with IV infusion of opioids. Neuraxial opioids are associated with side effects that could affect patients’ quality of recovery. Side effects include nausea and vomiting in more than 50% of patients and pruritus in up to 60%, as opposed to 15% to 18% for PCEA with local anesthetic or systemic opioids. Other adverse effects include urinary retention in up to 80% of patients and respiratory depression in 0.2% to 1.9%. These side effects are not limited to any specific opioid, and it is not clear whether their incidence is dose dependent. Both early and late respiratory depression can occur with neuraxial opioids. Most reported respiratory depression occurs with morphine because of its hydrophilic nature and cephalic CSF spread. PCEA with combined local anesthetic and neuraxial opioids results in a low incidence of respiratory depression that varies from 0.07% to 0.4%, thus making PCEA relatively safe to use in an unmonitored hospital setting.

Extended-Release Epidural Morphine

Extended-release epidural morphine (EREM) incorporates new technology in which microscopic particles consisting of numerous morphine-containing vesicles are each separated from adjacent chambers by naturally occurring lipid membranes. EREM provides a longer duration of postoperative analgesia than does traditionally available formulations but without the need for indwelling epidural catheters. Preliminary randomized controlled trials have indicated that EREM provides significant postoperative analgesia for up to 48 hours after hip and abdominal surgery. This modality appears to have a dose-dependent relationship for decreased oxygen saturation, with 20- and 25-mg doses being associated with higher rates of desaturation. Clinicians should not freeze, aggressively agitate, or shake the EREM vials. In addition, one should not administer any other agents in the epidural space around the time of EREM administration because an increased peak serum concentration of morphine may result. Side effects of EREM are mainly pruritus and respiratory depression, which requires treatment with opioid antagonists in 12.5% of patients.

Neuraxial analgesic agents, given as a single shot or as a continuous epidural infusion, provide effective postoperative analgesia (see Table 18.5 ). The choice of a particular technique should be made on an individual basis. The risks and benefits of a particular technique should be weighed for each specific patient.

Peripheral or Perineural Analgesia

The number of ambulatory procedures performed in North America has increased significantly, and the cost-saving benefit of minimizing patients’ hospital stays has gained importance. With the goals of same-day discharge, reduction in hospital length of stay, and improvement in postsurgical outcomes, many anesthesiologists routinely use multimodal analgesia with peripheral techniques. A variety of peripheral regional techniques can be used to enhance postoperative pain control while reducing side effects. Among these techniques are local anesthetic wound infiltration ; brachial, lumbar, and sacral plexus blocks; and nonepidural truncal blocks (paravertebral, transabdominal, and rectus sheath blocks). Peripheral analgesic techniques are important for facilitating cost savings in ambulatory surgery centers, especially when phase 1 recovery bypass is achieved and unplanned admissions are reduced. Peripheral regional analgesia delivered as a single injection or as a continuous infusion through a perineural catheter (PNC) provides analgesia superior to that with systemic opioids or epidural analgesia and is associated with minimal side effects, better rehabilitation, and shorter hospital stay. Use of a PNC in the lower extremity provides analgesia equal to that of an epidural with minimal side effects (hypotension, urinary retention, and inability to ambulate). Regardless of location, the analgesia provided through a PNC is superior to that of single-shot blocks, epidural analgesia, intra-articular analgesia, and IV PCA.

The number of complex orthopedic procedures such as joint replacement has increased tremendously in the last 2 decades and is expected to continue to increase as the population advances in age. Joint replacement, which is well known to improve a patient’s quality of life, typically causes severe pain in the immediate postoperative period and thus interferes with physical rehabilitation. Multimodal analgesia and the use of a PNC as the main techniques for control of pain have been shown to provide better analgesia, earlier passive joint movement, and earlier discharge home with adequate joint movement. A large series of hospital patients and outpatients treated with a PNC reported minimal clinician interventions and clinical adverse effects during treatment. With adequate instructions and phone access to health care providers, patients were able to manage their pain at home and remove the PNC without need for a hospital visit. More studies are needed before home use of a PNC becomes a widely applicable standard of care.

Techniques for peripheral single-injection or PNC analgesia vary among practitioners and include a paresthesia technique, peripheral nerve stimulation, and ultrasound-guided regional anesthesia (UGRA). Although evidence regarding the safety of UGRA is currently limited in comparison to what is known about nerve stimulation, it is becoming the technique of choice for most single-injection and continuous-infusion techniques.

Studies have shown that when compared with nerve stimulation, use of UGRA for upper or lower extremity blocks and placement of catheters offers a faster onset of sensory blockade and a greater block success rate. UGRA has also been shown to achieve faster block performance, require fewer needle passes, and induce less block-related discomfort, thus making this technique better received by patients.

Local anesthetics are the main analgesics used for peripheral blocks and in continuous-infusion catheters. Drugs with an intermediate duration of action, such as lidocaine and mepivacaine, are commonly used for blocks, whereas long-acting drugs such as ropivacaine, bupivacaine, and levobupivacaine are used mainly for continuous infusion. Some data suggest that bupivacaine and levobupivacaine are more potent than ropivacaine ; therefore, the ropivacaine concentration is often increased to compensate. However, ropivacaine, bupivacaine, and levobupivacaine have provided similar analgesic profiles in human trials.

Several medications are infrequently added to the local anesthetic to improve perineural analgesia. Although there are reports of opioids being added, insufficient evidence is available to draw any conclusion regarding the efficacy of this practice. Clonidine has been reported to prolong the duration of perineural analgesia, but randomized controlled studies have failed to demonstrate any clinical benefit. Epinephrine is commonly used in blocks to detect inadvertent intravascular injection, but it is rarely used in a continuous infusion because it causes prolonged vasoconstriction. Other adjuvants have been reported, but none are currently approved for perineural use in humans because of systemic side effects.

In summary,

• •
  

  Continuous neuraxial techniques provide superior analgesia and better patient outcomes, including those related to major morbidity.

  
  
• •
  

  Many factors affect the overall outcomes of continuous epidural analgesia, including the congruency of epidural catheter location and placement of the surgical incision and the type of analgesic regimen.

  
  
• •
  

  Neuraxial opioids provide postoperative pain control when administered alone or in combination with local anesthetics.

  
  
• •
  

  Peripheral or perineural regional techniques provide pain control superior to that with systemic opioids or epidural analgesia and are associated with minimal side effects.

  
  
• •
  

  Perineural continuous analgesia is beneficial in complex orthopedic procedures and is used as part of multimodal analgesia in the perioperative setting.

Brachial Plexus Blocks

Nerve conduction in the brachial plexus ( Fig. 18.3 ) can be blocked at many levels to provide anesthesia and postoperative analgesia during and after surgical procedures on the upper extremity ( Table 18.5 ). Use of UGRA may increase the overall success rate when compared with nerve stimulation or other methods. UGRA techniques for the brachial plexus may allow patients to receive the best anesthetic and analgesic effect with less local anesthetic volume and minimal side effects. An analysis of neurologic complications in 1000 UGRA procedures for elective orthopedic surgery showed that the rate of postoperative neurologic symptoms was very similar to that previously reported for traditional techniques. The incidence of nerve injury from a peripheral nerve block (PNB) has been estimated to be 0.4 per 1000 PNBs based on large prospective audits. Use of PNCs or perineural continuous infusion of local anesthetic is being advocated when prolonged analgesia of the arm is needed. PNCs could be used in the hospital setting or in an ambulatory setting as a home PNC. Insertion of a PNC may be facilitated by using paresthesia, nerve stimulation, or ultrasound guidance.

Brachial plexus anatomy.

(From Brown D. Atlas of Regional Anesthesia . Philadelphia: Saunders; 2010.)

Interscalene Block

The gold standard technique for shoulder and upper arm procedures is the interscalene block (ISB). The interscalene groove is commonly approached through an anterolateral technique. A posterior approach to the brachial plexus remains underused despite its effectiveness in securing a continuous interscalene block (CISB) catheter. The interscalene approach typically provides a complete block for the superior and middle trunk, but the inferior trunk is often blocked incompletely, thus making this approach unsuitable for forearm and hand procedures. For elbow procedures, the ISB is frequently supplemented by other nerve blocks such as the intercostobrachial, medial cutaneous and medial antebrachial cutaneous, and ulnar.

A single-injection ISB provides analgesia superior to that of systemic opioids. A reduction in verbal pain scale scores of greater than 50% and a reduction in total opioid requirement have been reported. CISB for shoulder surgery provides better analgesia than placebo or systemic opioids do and is associated with less opioid consumption and fewer opioid-related side effects. CISB with perineural infusion of local anesthetic has been shown to benefit patient rehabilitation and can be continued at home with a portable infusion pump. In a randomized controlled study, Ilfeld and colleagues showed that ambulatory CISB with perineural infusion of 0.2% ropivacaine decreased the time until readiness for discharge after total shoulder arthroplasty by allowing good shoulder range of motion and providing adequate pain control without parenteral opioids. When compared with ISB for moderate to severe outpatient shoulder procedures, 2-day CISB provided better pain control, reduced opioid requirements, improved sleep quality, and increased patient satisfaction. In the last decade, the UGRA technique for ISB has become more popular than the nerve stimulator technique. It provides a better block profile, has a faster onset and longer duration, requires fewer needles, and is associated with better patient satisfaction. Moreover, it has not sacrificed patient safety or increased the incidence of neurologic complications.

Concomitant phrenic nerve block occurs after brachial plexus block at the interscalene level, especially at the C6 level, because of its close proximity (2 to 4 mm) to the plexus. Blocking the brachial plexus at this level should be considered with great caution if a patient has respiratory insufficiency or chronic obstructive pulmonary disease. Some investigators have shown no difference in hemidiaphragmatic paresis after a reduction in local anesthetic volume of up to 10 mL at the ISB when ultrasound was used. Others are trying to identify the minimum effective local anesthetic volume necessary to provide postoperative analgesia with minimal side effects. Although the local anesthetic volume needed for ultrasound-guided ISB may be reduced, the optimal volume for analgesia still remains to be determined. For shoulder procedures, the addition of tramadol or dexamethasone as an adjuvant to local anesthetic prolongs the duration of analgesia.

Recently, different ultrasound approaches have been tried in an attempt to block the brachial plexus at the interscalene groove. No difference in block onset time or block quality was observed when intraplexus injection of local anesthetics or periplexus blocks were used. A low approach to the brachial plexus resulted in more distal spread of sensory and motor coverage than when the traditional approach was used.

Supraclavicular Block

The supraclavicular block is considered the spinal of the arm. This block is associated with the greatest blockade of the brachial plexus at the trunk and division level where all the trunks are compact and can be achieved with a single injection of local anesthetic. At lower volumes of local anesthestic, the supraclavicular block misses the dorsal scapular nerve, which arises from the root of C5, and also misses the superficial cervical plexus. Unless the local anesthesic tracks proximally toward the interscalene region, this block may be inadequate for shoulder surgery, but it provides adequate block for upper arm surgery. As with the ISB, supplemental blocks are required for elbow procedures (i.e., intercostobrachial). Of all the brachial plexus blocks, the supraclavicular block has the highest risk for pneumothorax, especially when done with the traditional “plumb bob” technique. Some recent studies have shown that the calculated volume of local anesthetic required for an ultrasound-guided supraclavicular block does not seem to differ from the conventionally recommended volume required for supraclavicular blocks performed with non–ultrasound-based nerve localization techniques. The minimum effective volume of 1.5% lidocaine with 5 µg/mL epinephrine was 32 mL. Multiple studies have confirmed that when UGRA is used, a single injection offers the same clinical profile and analgesic benefit as two injections.

Infraclavicular Block

Like the supraclavicular block, the infraclavicular block also approaches the brachial plexus where it is compact ( Fig. 18.4 ), at the level of the cords. This block can be used for procedures involving the elbow, forearm, and hand. It is especially useful in patients unable to abduct their shoulder to allow access to the axilla. A single injection or a continuous-infusion catheter placed with this technique provides effective analgesia. This approach also results in the most secure catheter insertion site of all brachial plexus blocks. This block has two main approaches—the traditional perivascular infraclavicular approach and the coracoid approach. They provide similar results, but the coracoid approach is associated with less risk for pneumothorax. For outpatient wrist and hand surgery, Hadzic and colleagues compared the use of a chloroprocaine infraclavicular nerve block with general anesthesia induced with volatile agents. They found that general anesthesia with volatile agents led to increased postanesthesia care unit admissions (vs. phase 1 recovery bypass), higher reports of postoperative pain, longer time to ambulation, and longer time to same-day discharge. Chelly and coworkers stated that PNB catheters are probably indicated for implantation procedures after trauma, as well as for open reduction and internal fixation of the hand or digits, although a prospective randomized trial to definitively verify this intuitive concept may be difficult to conduct. Ilfeld and colleagues showed that use of a continuous infraclavicular brachial plexus catheter resulted in less postoperative dynamic pain and opioid consumption and fewer sleep disturbances than did placebo catheter infusion. The surgical procedures performed included open reduction and internal fixation (elbow, radius, or ulna), bony and capsular wrist procedures (carpectomy, capsulodesis, fusion, or shrinkage), metacarpal arthroplasty, suspensionplasty, and ulnar nerve transposition.

Infraclavicular anatomy.

(From Wells M. Local and Regional Anaesthesia in the Emergency Department Made Easy . Philadelphia: Churchill Livingstone; 2010.)

An infraclavicular brachial plexus block for regional anesthesia of the lower part of the arm has efficacy comparable to that of other brachial plexus blocks. This block has a lower likelihood of tourniquet pain during surgery and provides more reliable blockade of the musculocutaneous and axillary nerves than does a single-injection axillary block. Many investigators have confirmed that when using UGRA for an infraclavicular block, a single injection of local anesthetic posterior to the axillary artery is as effective as multiple injections. A randomized comparison of infraclavicular and supraclavicular PNCs for postoperative analgesia showed that local anesthetic infusion via an infraclavicular PNC provides analgesia superior to that via a supraclavicular PNC.

Axillary Block

This block produces the most effective block for all surgical procedures on and distal to the elbow, but it requires supplementation for the tourniquet (intercostobrachial, medial brachial cutaneous, and medial antebrachial cutaneous) if it is to be used as a surgical block. Axillary blocks have been shown to reduce postoperative pain scores by more than 50%, decrease the total in-hospital opioid requirement, and lengthen the time until the first analgesic dose. The axillary sheath at this level is often discontinuous, and the block should target the individual terminal branches. A nerve stimulator can be used to identify all the individual components and to obtain a consistently effective block. A small study demonstrated that each terminal branch can be targeted under ultrasound guidance with as little as 1 mL of 2% lidocaine with 1:200,000 epinephrine per nerve to provide a fast onset and surgical anesthesia. The traditional transarterial and single-injection techniques can often miss the musculocutaneous nerve (C5-6); therefore, that nerve should be specifically sought and blocked. It can be visualized in the corocobrachialas muscle and traced proximally to the axillary artery under ultrasound guidance.

Intravenous (Bier) Block

The mechanism of IV regional anesthesia (IV RA) is generally accepted to involve diffusion from veins to small nerves and nerve endings after exsanguination. IV regional blocks for the upper extremity, which use a proximal arm tourniquet or double tourniquet, have been well described. IV regional blocks for the lower extremity have been reviewed as well. Traditional IV regional techniques that use a single- or double-tourniquet technique for the lower extremity may carry a high failure rate, in which case supplementation by the surgeon or conversion to general anesthesia is required. Of potential interest, however, is an intercuff technique for IV RA that has been developed for use in knee surgery in an effort to produce better localization and reduce overall dosing requirements.

Opioids (other than meperidine, 30 mg or more) are generally considered not to be beneficial when given via the IV regional technique ; systemic side effects of meperidine are manifested at the 30-mg threshold. Tramadol, 100 mg, administered as IV RA with lidocaine is associated with a self-limited rash below the tourniquet and does not necessarily confer an analgesic benefit. In addition, tramadol has not been shown to improve block or postoperative analgesic quality when coadministered with ropivacaine.

Less controversial additives to IV RA appear to have the potential to provide intraoperative tourniquet tolerance, postoperative analgesia, or both. Ketorolac can achieve both end points when the tourniquet is applied to both the upper and lower parts of the arm. Its use for this purpose is generally accepted, with no basis at this time for exceeding a 20-mg dose in adults. Clonidine at a dose of 1 µg/kg is accepted to improve tourniquet tolerance and reduce postoperative analgesic requirements with minimal side effects. Dexmedetomidine (0.5 mg/kg) has also shown benefit. Ketamine at a dose of 100 µg/kg has also been shown to improve tourniquet tolerance and reduce postoperative analgesic requirements in a manner that appears to be more potent than 1 µg/kg clonidine. When compared with plain lidocaine, dexamethasone (8 mg) was recently shown to reduce postoperative analgesic requirements during the first 24 hours after surgery. Given the multiple mechanisms that contribute to postoperative pain, the logical future study would involve a step-function assessment of serial additives and combinations of ketorolac, clonidine or dexmedetomidine, ketamine, and dexamethasone. The coadministered local anesthetic (0.5% lidocaine or 0.1% to 0.2% ropivacaine) is unlikely to influence results with respect to duration of postoperative analgesia beyond the recovery room period.

Complications with IV RA are very uncommon. Seizures have been reported after deflation of the tourniquet with a tourniquet time as long as 60 minutes and with lidocaine at its lowest effective dose (1.5 mg/kg). Several cases of compartment syndrome have also been reported.

In summary,

• •
  

  Interscalene analgesia is the gold standard technique for shoulder and upper arm procedures. Phrenic nerve paresis is a common side effect.

  
  
• •
  

  Supraclavicular analgesia is considered the spinal of the brachial plexus. It provides an adequate block for upper arm surgery; supplemental blocks are required for elbow procedures. It is associated with a risk for pneumothorax.

  
  
• •
  

  Infraclavicular analgesia can be used for procedures involving the elbow, forearm, or hand. It provides the most secure catheter insertion site.

  
  
• •
  

  Axillary analgesia produces the most effective block for all surgical procedures on the elbow, forearm, and hand. Supplemental blocks are required, especially musculocutaneous.

  
  
• •
  

  IV (Bier) regional analgesia is well described in the upper extremity but used less frequently in the lower extremity.

Lower Extremity Blocks

For patients undergoing surgical procedures on the lower extremity, nerve conduction in the lumbar and sacral plexuses can be blocked at many levels for anesthesia and postoperative analgesia ( Table 18.6 ). The nerve supply to the lower extremity is derived from two nerve plexuses arising from the ventral rami of the spinal nerve roots of the lower spinal cord ( Fig. 18.5 )—the lumbar plexus (L1-4) and the sacral plexus (L4-5, S1-3). The lumbar plexus gives rise to the femoral nerve (L2-4), the obturator nerve (L2-4), the lateral femoral cutaneous nerve (L2-3), and three other branches that supply the inguinal and genital areas (iliohypogastric, ilioinguinal, and genitofemoral nerves). The sacral plexus gives rise to the sciatic nerve (L4-5, S1-3) and provides branches that supply the musculature around the hip and pelvis.

Table 18.6

Lower Extremity Block Considerations

Technique	Agents	Indication	Considerations and Comments
A: Lumbar plexus block B: Continuous infusion	All lower extremity blocks except Bier blocks are amenable to most LAs. Choice of agent based on duration of anesthesia and postoperative analgesia	A: Procedures on the hip, thigh, and knee. B: Procedures on the hip, thigh, femur, and knee requiring prolonged analgesia	Reliable way to block the femoral, lateral femoral cutaneous, and obturator nerves with a single injection NS- or US-guided techniques Ensure a quadriceps twitch without a foot twitch and without an obturator (hip adduction) twitch to reduce the chance of unwanted epidural spread Cause weakness of the psoas muscle (hip flexion) and hip adduction The fascia iliaca is the anterior approach for LPB
A: Femoral block B: Continuous infusion	A: Choice of agent based on goal duration of anesthesia and analgesia B: Ropivacaine 0.2% or bupivacaine 0.125% ± opioid	A: Procedures on the anterior aspect of the thigh, femur, and knee B: Procedures on the anterior aspect of the thigh, femur, and knee requiring prolonged analgesia	Simple and easy to perform Commonly combined with sciatic single-injection or catheter techniques NS- or US-guided techniques Preserves hip adduction and psoas-mediated hip flexion
Saphenous nerve		Procedures on the knee and medial aspect of the ankle Saphenous (midthigh) used with knee procedures	Sensory continuation of the femoral nerve Supplies the medial aspect of the leg, ankle, and foot US-guided techniques or subcutaneous infiltration
Obturator nerve		Infrequently used in knee arthroplasty Bilateral obturator is used for urologic procedures	Gives motor branches to the adductors of the thigh, sensory branches to medial part of the thigh, and less than 5% to the knee joint
A: Proximal sciatic approaches B: Continuous infusion		A: Procedures on the hip, posterior aspect of the thigh, and posterior aspect of the knee B: Procedures on the hip, posterior aspect of the thigh, and posterior aspect of the knee requiring prolonged analgesia	Approaches include parasacral, gluteal (e.g., Labat), subgluteal, lateral, and anterior NS- or US-guided techniques Parasacral and gluteal approaches used for hip procedures Subgluteal used for knee procedures Cause hamstring weakness
A: Distal sciatic approaches B: Continuous infusion		A: Procedures below the knee and ankle B: Procedures below the knee and ankle requiring prolonged analgesia	NS- or US-guided techniques Common peroneal and tibial blocked at the bifurcation Avoid hamstring weakness

LA, local anesthetic; LPB, lumbar plexus block; NS, nerve stimulator; US, ultrasound.

Lower extremity anatomy.

(Courtesy of Mayo Foundation.)

Lumbar Plexus Block

Because the main nerves supplying the hip joint are the femoral and obturator nerves, this block (either single shot or continuous infusion) provides adequate postoperative analgesia for procedures involving the hip joint, including total joint replacement and repair of hip fractures. In a randomized clinical trial of patients undergoing hip hemiarthroplasty under general anesthesia, Turker and colleagues compared the use of continuous infusion from a lumbar plexus catheter with the use of an epidural catheter. They found that patients who received a lumbar plexus catheter had less motor block, ambulated sooner, and experienced significantly fewer overall complications. More than a decade ago investigators reported that for patients undergoing total hip arthroplasty, those who received lumbar plexus single-injection blocks had less pain and less blood loss during and after surgery than did those who did not receive the block. Others reported that in elderly patients with hip fractures, those who received lumbar plexus and parasacral blocks (vs. general anesthesia) exhibited significantly less hypotension during surgery, had fewer intensive care unit admissions (0/30 vs. 11/30), and had a shorter length of hospital stay (7 vs. 14 days).

A lumbar plexus block also provides excellent postoperative analgesia for most invasive knee procedures such as anterior cruciate ligament (ACL) reconstruction, multiligament reconstruction, or total knee arthroplasty (TKA). Matheny and colleagues found that the opioid requirement after arthroscopic ACL reconstruction was 89% lower in the group that received a continuous lumbar plexus block than in those who had IV PCA. However, a femoral nerve block in the groin is much simpler and easier to perform than a lumbar plexus block and provides equally efficacious analgesia for invasive knee procedures in which obturator nerve coverage is not relevant. In a randomized triple-masked trial, Ilfeld and colleagues compared the use of an overnight lumbar plexus catheter with use of the catheter for four nights in patients who had undergone hip arthroplasty. They found that use of the catheter for four nights decreased the time that patients needed to reach discharge criteria by 38% but did not significantly increase ambulation distance.

Femoral Nerve Block

Like the lumbar plexus block, a femoral nerve block provides excellent postoperative analgesia for invasive procedures around the knee (excluding the posterior aspect of the knee). Unlike the lumbar plexus block, a femoral nerve block preserves hip adduction and psoas-mediated hip flexion. A femoral block must often be supplemented with a single-shot or continuous sciatic nerve block for procedures such as TKA or ACL reconstruction with a hamstring autograft. Many randomized controlled studies that have compared UGRA, peripheral nerve stimulation, and loss-of-resistance techniques for the femoral nerve suggest that the ultrasound technique could offer faster onset of sensory loss and longer analgesia with less local anesthetic volume.

In the late 1990s, two studies from Europe examined rehabilitation outcomes after total knee replacement when a continuous femoral block (CFB) was used. When compared with IV PCA, CFB led not only to better pain relief but also to significantly better knee flexion, faster achievement of ambulation goals, and overall faster convalescence. Patients who received CFB infusions experienced fewer side effects than did epidural patients in both studies, and patients in the CFB groups were discharged home from inpatient rehabilitation units 20% sooner than were patients in the IV PCA groups.

In the United States, a similar anesthetic treatment method was applied to patients undergoing total knee replacement. All patients underwent general anesthesia and were randomized to receive IV PCA, epidural infusion, or single-injection femoral-sciatic blocks followed by a continuous femoral infusion. Continuous femoral infusion patients (vs. IV PCA patients) had a 72% reduction in postoperative bleeding ( P = 0.05), achieved better performance on continuous passive motion, had a 90% decrease in serious complications (including less blood loss), ambulated sooner (2.5 vs. 3.5 days), and had a 20% decrease in the length of hospitalization (4 vs. 5.5 days). In 2010, a meta-analysis of 23 randomized controlled trials showed that a femoral nerve single block or continuous infusion provides better analgesic outcomes after TKA than does IV PCA. A continuous femoral nerve block after TKA was associated with lower opioid consumption and better functional recovery at 6 weeks than periarticular infiltration was.

A continuous femoral nerve block is an acceptable analgesic alternative to a continuous posterior lumbar plexus block for hip arthroplasty when a stimulating PNC is used. However, patients who receive continuous femoral catheters might experience more motor block, thus making ambulation suboptimal.

Fascia Iliaca Block

The fascia iliaca compartment block was mainly described for the pediatric population in 1989 and was widely reported to provide good analgesia for hip and knee procedures in adolescents and adults. In 2008, Dolan and colleagues compared the use of UGRA for this block with the traditional fascial loss of resistant (LOR) technique for postoperative analgesia in hip and knee arthroplasty. They found that when compared with the LOR technique, use of UGRA significantly increased the block success rate, especially at the medial aspect of the thigh (95% versus 60%), and increased the percentage of patients in whom the femoral, obturator, and lateral cutaneous nerves were all completely blocked (82% vs. 47%).

Sciatic Nerve Block

Proximal sciatic nerve blocks are most often used as an adjunct to femoral or lumbar plexus blocks for painful procedures around the hip or knee, as discussed earlier, but they can also provide excellent analgesia for all major foot and ankle procedures (especially when a thigh tourniquet is planned).

In patients undergoing TKA, continuous sciatic nerve blocks provide greater analgesia, decrease morphine request, and improve early rehabilitation when compared with the use of single-injection sciatic nerve block or lumbar plexus blocks. Studies that have examined subgluteal continuous sciatic nerve blockade for orthopedic ankle and foot surgery have reported significant reductions in visual analog pain scores. Similarly, continuous sciatic nerve blockade has shown significant analgesic benefit in patients undergoing below-knee amputation. Use of a proximal sciatic nerve block for distal foot and ankle procedures is often limited by concerns of hamstring muscle weakness.

Studies that have compared UGRA of the sciatic nerve with peripheral nerve stimulation techniques have shown that UGRA has a higher sensory block success rate and requires less local anesthetic and less time to perform. Insufficient data are available to compare the block failure rate and the actual duration of sensory blockade between the two techniques.

Popliteal Fossa Sciatic Nerve Block

The nerve can be blocked from the posterior or lateral approach, although the lateral approach may be superior when there are concerns regarding patient positioning. A popliteal fossa block provides effective postoperative analgesia for all foot and ankle procedures (assuming that the saphenous nerve is concomitantly blocked). It also preserves hamstring function, thus facilitating ambulation.

Effectiveness of the popliteal sciatic block for outpatient foot and ankle procedures was demonstrated by McLeod and colleagues. They compared the lateral popliteal fossa block with an ankle block and with subcutaneous infiltration of local anesthetics. The popliteal fossa block provided longer postoperative analgesia. When the UGRA technique is used, blocking the tibial and common peroneal nerves in the popliteal fossa separately at the bifurcation provides a faster onset than does a prebifurcation sciatic block.

Continuous popliteal sciatic nerve catheters were first introduced by Singelyn and colleagues, who described a challenging Seldinger (catheter-over-guidewire) technique for catheter placement and achieved a 92% success rate. Since then, authors have repeatedly found that continuous-infusion nerve blocks lead to excellent analgesic outcomes when compared with single-injection blocks or placebo catheters. Ultrasound guidance may reduce the time required for placement of popliteal-sciatic PNCs and result in fewer placement failures than when stimulating catheters are used, but analgesia may be mildly better with successfully placed stimulating catheters. Patient satisfaction with block placement was also higher with ultrasound guidance than with the nerve stimulation technique. Adding continuous femoral catheter infusion of ropivacaine to continuous popliteal catheter infusion improved postoperative analgesia during movement after major ankle surgery. This effect was still present 6 months after surgery.

In summary,

• •
  

  The nerve supply to the lower extremity comes from the lumbar plexus and the sacral plexus.

  
  
• •
  

  Lumbar plexus analgesia provides excellent postoperative analgesia for most invasive hip and knee procedures. It is considered a high-risk block.

  
  
• •
  

  Femoral nerve analgesia provides excellent postoperative analgesia for invasive knee procedures; it is relatively noninvasive and safe.

  
  
• •
  

  A fascia iliaca block is performed via an anterior approach to the lumbar plexus.

  
  
• •
  

  The sciatic nerve can be blocked at various sites along its course (parasacral, subgluteal, and popliteal) to provide analgesia below the knee joint.

Continuous Wound Infusion of Local Anesthetics

The mechanisms of action of local anesthetic wound infusions include blockade of nociceptive transmission from the wound surface, inhibition of the local inflammatory response to surgical injury, and spinal cord suppression from systemic absorption of local anesthetics. Recently, special wound infusion catheters have become available that can be placed intraoperatively into the wound under direct supervision of the surgeon to infuse local anesthetics, and use of such a technique is an acceptable option as part of multimodal postoperative analgesia.

A systematic review of randomized trials that examined the use of continuous wound catheters in multiple surgical procedures consistently demonstrated analgesic efficacy in terms of reduced pain scores and opioid use for all surgical subgroups examined. A total of 39 randomized controlled trials (1761 patients) were included in the final analysis. Overall, when compared with placebo, local anesthetic infusions resulted in a significant decrease of approximately 33% in pain scores of patients both at rest and with activity. Subgroup analysis confirmed the decreased pain scores in patients undergoing all types of surgical procedures except for abdominal surgery. When compared with subjects given placebo, those who were randomized to receive subcutaneous infusions of local anesthetics demonstrated reduced need for opioid rescue and decreased daily opioid consumption, which may have contributed to a reduction in the incidence of nausea in the continuous wound catheter group (21% vs. 39%, odds ratio = 0.42, 95% confidence interval = 0.27 to 0.67). When compared with epidural morphine, continuous wound infusion with ropivacaine for 48 hours after cesarean delivery was associated with better analgesia, lower incidence of side effects, and shorter hospital stay. PCEA with opioids and local anesthetics was superior to patient-controlled local anesthetic wound infusion for laparotomy. The incidence of side effects was similar in both groups.