C H A P T E R zzzzzzzzzzzzzzzzzzzzzzzzzzz

7
Pain Management following Traumatic Injury

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Frederick W. Burgess, M.D., Ph.D. Richard A. Browning, M.D.

With rare exception, painful sensations are a common experience in life. In the scheme of survival, pain represents the bodys early warning system indicating that attention must be paid to the inciting problem. In most cases, the intensity of the pain dictates immediate action, such as immobilization of the injured area. This innate response prevents the likelihood of further injury and potentially improves survival by allowing time for healing. Unfortunately, pain can also adversely affect survival, particularly during the postinjury recovery phase. Persistent pain leading to prolonged immobilization may lead to thrombotic events, muscle wasting, restriction in range of motion, pulmonary infection, and even death. In addition to these physiologic consequences, there can also be a signicant emotional cost to the pain that is associated with traumatic injury. Although of less concern during the immediate evaluation and treatment of the patient with multiple injuries, the emotional impact of pain can be considerable. Most patients do not fully comprehend the extent and nature of their injuries but interpret poorly controlled pain as an indicator of serious injury. The emotional distress and accompanying anxiety that they feel is heightened by inadequate pain control and contributes to an emotionally out-of-control patient. Initial pain treatment may, by necessity, be administered cautiously, but it should not be forgotten. Accompanying family members may also be distressed and tend to focus on the patients pain complaints rather than the more life-threatening aspects of their injuries. Judicious use of analgesics may facilitate the evaluation process and improve the sense of well-being in the patient and family. This chapter reviews the physiology of pain and attempts to provide a framework for the range of therapeutic options for optimal pain treatment of the trauma victim.

WHY TREAT PAIN?

zzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzz Pain is by far the major reason for most patient visits to a physician. In most circumstances, the ultimate resolution

of the painful condition is dependent on identication and resolution of the underlying inciting factor. In the case of skeletal trauma resulting in a fracture, realignment and splinting of the fracture will reduce the pain but not necessarily eliminate it in the short term. Healing is an inammatory process that produces a sensitization of the nervous system that contributes to central and peripheral pain generation.14, 49 Traumatic injury, whether by accident or the surgeons scalpel, can be accompanied by a more generalized inammatory or stress response that disturbs the bodys normal homeostasis.41 The extent to which the stress response alters the patients physiology depends in part on the location(s), severity, and preexisting physiologic impairments. For example, patients with a history of peripheral vascular disease, coronary artery disease, and tobacco use are at high risk for perioperative thrombotic events. Their propensity for clot formation is escalated following surgical trauma, triggered in part by the perioperative stress response, which promotes the formation of various acute phase reactants.5, 32, 42 One such substance is tissue plasminogen activator inhibitor (t-PAI), which promotes blood clot formation by inhibiting the thrombolytic action of plasmin. Following surgery, t-PAI levels are elevated and may contribute to myocardial infarction, pulmonary embolism, and peripheral arterial revascularization failure.32 The stress response to surgery can be blunted through the use of regional anesthesia, such as epidural anesthesia, and the aggressive use of postoperative analgesia, which can improve patient outcome.5, 52 Recent improvements in our understanding of how painful sensations are conducted and amplied by the nervous system have led to a greater emphasis on early and aggressive perioperative pain control. Pain signals are initiated through the direct stimulation and indirect sensitization of peripheral thermal and mechanical receptors. Local tissue trauma generates a cascade of prostaglandin and kinin substances that promote a lowered threshold for stimulation in the C-type bers of the surrounding tissues. This process contributes to the hyperalgesia and hyperesthesia associated with tissue trauma and ultimately
147

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SECTION I General Principles

contributes to the release of several excitatory neurotransmitters within the dorsal horn of the spinal cord, where the peripheral afferent neuron synapses with the second-order neuron.49 In the dorsal horn of the spinal cord, peptides, such as substance P, and excitatory amino acids, such as glutamate, are released from the primary afferent neuron onto the second-order sensory neuron. These second-order nociceptive neurons, or wide dynamic range neurons, become sensitized through the action of substance P on the NK-1 receptorlinked sodium channels, and glutamate on the N-desmethyl-D-aspartate receptor linked to a calcium channel, as illustrated in Figure 71.8, 49 Repetitive C-ber stimulation promotes a central sensitization of the secondorder neuron, facilitating the transmission of pain impulses to the thalamus and cortical regions of the brain. This facilitation of central nociceptive transmission is referred to as wind-up. Thus, sustained painful stimuli are capable of triggering sensitization of nociceptive signals, both in the periphery and within the central nervous system. Recent evidence generated from animal models and human clinical trials suggest that early multimodal analgesic interventions improve perioperative pain control and ultimately reduce the duration of postoperative pain.30, 43, 51 Combined treatment with nonsteroidal antiinammatory drugs (NSAIDs), opioids, and local anesthetics provides immediate pain relief, and, when used in combination, reduces analgesic side effects. A review of

available drugs and strategies for combined drug therapy follows.

NONSTEROIDAL ANTIINFLAMMATORY DRUGS

zzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzz The NSAIDs are an important mainstay of analgesic therapy in orthopaedic medicine. Since the synthesis of acetylsalicylic acid in 1899, the NSAIDs have evolved into the most widely prescribed oral analgesic medication. Unfortunately, the value of this analgesic class is too often forgotten in the management of the acute trauma and postoperative patient. Avoidance of NSAIDs in these settings is directly attributable to concerns over the potential for bleeding complications. These concerns are largely overstated, as demonstrated in the postmarketing surveillance data collected for ketorolac.40 Their data revealed a minimal risk of perioperative bleeding at the surgical site following perioperative ketorolac administration. Despite this, many physicians and surgeons continue to advise their preoperative patients to discontinue the use of NSAIDs before surgery. As previously indicated, there is a clear rationale for prescribing a NSAID on the day of surgery.6 The NSAIDs produce their analgesic action through the inhibition of cyclooxygenase synthetase at the site of injury in the periphery and possibly through actions within the central nervous system. Tissue trauma liberates phospholipids from damaged cellular membranes, which are in turn converted by phospholipase into arachidonic acid. Cyclooxygenase converts the arachidonic acid into prostaglandin precursors that are responsible for the development of regional pain, edema, and vasodilatation. Within the central nervous system, prostaglandins appear to have a role in the transmission of pain signals, independent of their peripheral inammatory actions. Animal and clinical data have demonstrated a potent central analgesic effect of NSAIDs when delivered intraspinally.23, 25 The importance of this central mechanism to the analgesic effects of most NSAIDs is uncertain but may provide a useful target for future analgesic development. There are a large number of different NSAIDs currently on the market. Fortunately, it is not necessary to become familiar with every agent. NSAID selection may be made on the basis of duration of action desired and on the side effect tolerance prole. The most potent anti-inammatory effect is provided by indomethacin; however, adverse reactions and side effects have led to a decline in the use of this compound. For short-term therapy, ibuprofen remains one of the least expensive and best-tolerated NSAIDs. The one disadvantage of ibuprofen is its short duration of action, which creates a need for multiple daily doses (Table 71). Even with pain relievers, compliance can be a problem, often resulting in poor pain control and dissatisfaction with the treatment. Longer acting agents, such as naproxen or piroxicam, offer greater convenience of dosing but appear to carry a greater risk of gastrointestinal bleeding and ulceration.21 This increased risk of gastric perforation and bleeding may relate to the sustained inhibition of the cyclooxygenase enzyme provided by the

Opioids Presynaptic receptors Postsynaptic receptors

Gene induction

AMPA
Print Graphic

Glutamate NMDA

Prostanoids Nitric oxide Wind up Hyperalgesia

Presentation

Peptides Substance P CGRP Neurokinin A

C-fiber
FIGURE 71. Excitatory amino acids and peptides released onto the wide dynamic range neuron, located in the dorsal horn of the spinal cord, produce a state of excitation. This excitation process will facilitate the transmission of pain signals to the brain.

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CHAPTER 7 Pain Management following Traumatic Injury TABLE 71

149

Nonsteroidal Anti-inammatory Agents

Agent Acetylsalicylic acid Choline magnesium trisalicylate NONSELECTIVE COX INHIBITORS Ibuprofen Naproxen Naproxen sodium Ketoprofen Indomethacin Ketorolac Diclofenac Piroxicam Etodolac Nabumetone COX-2 SELECTIVE Celecoxib Rofecoxib Meloxicam

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Dose Range (mg) 325650 10001500 200800 250500 275550 2550 2550 1560 i.m. 10 p.o. 50 2040 200500 5002000 100200 2550 7.515 Dosing Interval (hr) 46 12 48 68 68 68 812 6 8 24 612 1224 12 1224 24 Maximum Dose (mg) 40006000 20003000 2400 1250 1375 300 100 120 150 40 1000 2000 400 50 15 Half-life (hr) 2030 minutes 917 22.5 1215 1215 1.5 2 6 12 50 7 24 11 17 2024

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prolonged half-lives of these drugs. Ketorolac deserves mention because it is the only NSAID available for parenteral delivery in the United States, making it convenient for intraoperative and postoperative administration. Unfortunately, ketorolac has received a black box warning by the U.S. Food and Drug Administration to limit parenteral administration to no more than 5 days. This resulted from postmarketing data that revealed an increase in gastrointestinal bleeding when ketorolac was administered parenterally for more than 5 days.40 Associated risk factors included age older than 70 years and concomitant medical illness.39 under study and may supplant the use of ketorolac during the perioperative period. Although the COX-2 inhibitors represent a major step forward in safety, several important points must be emphasized. COX-2 inhibitors are safer than the nonselective COX inhibitors, but they do not provide better analgesia or anti-inammatory effect. Thus, in circumstances in which a less expensive nonselective agent for a short-term course of therapy is acceptable, the nonselective COX inhibitors remain the best choice for the sake of economy. Also, the selective COX-2 inhibitors are not entirely devoid of the potential for gastrointestinal ulceration.22, 35, 36 Among patients with known peptic ulcerations, the COX-2 inhibitors should be avoided. COX-2 is a component of the healing response and can be identied in healing ulcers. Administration of a COX-2 inhibitor in this setting interferes with the healing process and can contribute to further injury and perforation. The COX-2 inhibitors cannot be used with impunity, particularly in the long-term setting. Finally, the COX-2 inhibitors have the potential to impair renal function.33 This will be most pronounced in the elderly or the volume-depleted patient. Peripheral edema and renal failure may accompany their use and should be monitored carefully in the high-risk patient. For the perioperative patient, combining a NSAID with an opioid can result in a 30% to 40% reduction in opioid requirement.13, 48 Rarely will a NSAID provide adequate analgesia as a solitary analgesic, but as a component of a combined analgesic regimen, it can improve the quality of pain relief and reduce opioid-related side effects.4, 13, 37, 48 The opioid-sparing effect is most evident in the orthopaedic and dental surgery populations. The advantage of combining a NSAID with an opioid may become evident in a faster return of bowel function, less constipation, less nausea, and improved analgesia.13, 48 Parenteral ketorolac has been shown to be a useful adjuvant to epidural opioid analgesia.4, 37 With the availability of the COX-2 inhibi-

Selective Inhibition of Cyclooxygenase

Cyclooxygenase exists as two isoenzymes.38 Cyclooxygenase-1 (COX-1) is a constitutive enzyme, which is continuously expressed in many tissues, including the gastric mucosa, platelets, and kidney. A second isoenzyme, cyclooxygenase-2 (COX-2), is an inducible enzyme usually associated with inammation and healing.38 It is now possible to selectively target the COX-2 enzyme for inhibition, which can greatly reduce unwanted effects on platelet function and the mucosal integrity of the gastrointestinal tract.17 Preliminary data from studies on two new COX-2 selective compounds, celecoxib and rofecoxib, reveal a much lower risk of gastric erosion and ulceration relative to nonselective COX inhibitors such as ibuprofen and naproxen.22, 34, 35 Furthermore, celecoxib and rofecoxib do not appear to affect platelet function. They are devoid of the antiplatelet effects that are associated with COX-1 inhibition.17 The COX-2 selective inhibitors may be particularly advantageous during the perioperative period, because they do not need to be discontinued and may be administered on the day of surgery to provide perioperative analgesia. Paracoxib, the prodrug form of valdecoxib, a parenteral COX-2 inhibitor, is currently

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SECTION I General Principles

tors, more widespread use of NSAIDs during the perioperative period should result in improved analgesia. The lack of platelet interference allows the COX-2 inhibitors to be administered very early in the treatment of the orthopaedic trauma patient, provided careful consideration of renal perfusion and volume resuscitation issues has occurred.

a reduction in glomerular blood ow, which may be further aggravated by the addition of a NSAID, leading to acute renal failure. HEPATIC TOXICITY Although chemically very different, the NSAIDs as a class appear to carry some risk of hepatotoxicity. Two agents in particular have been linked to hepatic injury, necessitating routine monitoring. Bromfenac, which has been withdrawn from the U.S. market, was linked to hepatic failure. Diclofenac has been associated with a hepatitis-type syndrome. Other NSAIDs have been linked to hepatic injury, but as with many drugs undergoing clinical trials, it is not always clear whether there is a direct relationship. Any patient at risk or having a history of liver disease should be evaluated periodically. BRONCHOSPASM As a class, the NSAIDs may contribute to the aggravation of asthma. Individuals sensitive to aspirin-induced bronchospasm and those who have nasal polyps should probably avoid the NSAIDs. HEMATOLOGIC TOXICITY The well-known potential for aspirin and the NSAIDs to interfere with platelet aggregation has been exploited as a means to prevent perioperative thrombotic complications. However, in the wrong setting this anticoagulant effect may be disastrous. With the availability of the COX-2 selective NSAIDs, the antiplatelet effects have been eliminated. There is still some slight potential for modest prolongation of the prothrombin time in patients receiving warfarin for anticoagulation; however, this effect appears to be small and can be readily compensated for, if necessary.

Hazards
As alluded to previously, the NSAIDs carry the potential for numerous side effects and adverse reactions. Most of the adverse effects of the NSAID class can be anticipated and monitored. The relative risk-to-benet ratio of any medication should be explained to the patient. This approach helps to include the patient in the decisionmaking process, provides informed consent, and improves early recognition of any developing problems. GASTROINTESTINAL TOXICITY There are two forms of gastrointestinal problems associated with the NSAID class. Many patients encounter dyspepsia on starting a course of NSAID therapy. This effect represents a topical irritant effect of the medication and does not herald peptic ulcer formation or gastric perforation. In most cases, this effect fades with continued use and adaptation. It may also be reduced by encouraging the consumption of food along with the NSAID. Often, more serious gastrointestinal damage is not heralded by dyspepsia but instead may manifest as a perforated viscus without prodrome or as a spontaneous hemorrhage.16 The NSAIDs interfere with the protective generation of mucous and bicarbonate, leading to ulceration of the duodenal region. Concomitant administration of histamine antagonists, proton inhibitors, and misoprostol appears to be somewhat helpful but cannot completely prevent ulcerations.15 As a general statement, patients with known peptic ulcer disease should not be treated with a NSAID. Patients with a history of peptic ulcer disease, without active ulcers, must be treated cautiously. The combination of a COX-2 selective inhibitor in conjunction with a cytoprotective agent, such as misoprostol, may be a reasonable approach. However, to our knowledge, there are no data that support this assumption. RENAL TOXICITY Adverse renal effects of the NSAID class include impaired renal perfusion, sodium retention secondary to reduced glomerular ltration, peripheral edema, congestive heart failure, hyperkalemia, interstitial nephritis, and nephrotic syndrome. Acute renal failure, peripheral edema, and heart failure are all interrelated and can often be anticipated from the patients medical history. Treating any patient with hypertension, a known history of congestive heart failure, or preexisting renal impairment must be undertaken with caution. Some assessment of renal function should be made before initiating therapy. This is also true with respect to the trauma patient. Hypovolemia produces

THE OPIOIDS

zzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzz When one views the incredible developments that have contributed to modern medicine, it is striking to note how little we have improved with respect to analgesia. The tools of analgesialocal anesthetics such as cocaine, the NSAIDs such as the salicylates, and the opiate alkaloids such as morphinehave been used by various cultures throughout recorded history. Unfortunately, our pharmacologic approaches have not improved over the past thousand years. Renements in our understanding and improvements in the purity of analgesic compounds have occurred, but in essence we still have the same tools used by the ancient cultures. Opiate analgesics have been the mainstay of analgesic therapy since before recorded history and continue to be the most important category of analgesic medication. Opioids, a term that includes natural opiate compounds derived from the poppy plant and synthetic compounds, produce their analgesic effect by activating one or more opiate receptors. The opiate receptors are the binding sites

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CHAPTER 7 Pain Management following Traumatic Injury

151

for an endogenous group of peptides, which includes the endorphins and the enkephalins. Additional peptides and receptors have been discovered, but their contribution to pain and analgesia are still being sorted out. Currently, there are three opioid receptors of clinical importance, mu, kappa, and delta, revealing evidence of selective binding for specic endogenous peptides and to some extent, exogenous compounds. The most important of these receptors appears to be the mu receptor. This is the principle binding site for most of the clinically useful exogenous opioids and mediates the analgesic and respiratory depressant effects of the opioid agonists. Most of the currently available opioids activate multiple receptor types; at present, there are no clinically useful receptor selective compounds available for patient care. As a general statement, any one of the full agonist opioids can be effective in managing acute pain, provided the opioid is delivered in an effective dose range appropriate to the route of delivery. Obtaining adequate analgesia often depends on striking a balance so that the patient experiences pain relief without suffering from side effects. For patients with severe acute pain, health care providers often must walk a tightrope between patient comfort on the one side and somnolence and respiratory depression on the other. Too often physicians and nurses restrict pain medication for fear of causing unwanted side effects, leaving the patient with an unacceptable level of pain.26 Another barrier to adequate analgesia may be attributed to the poor understanding or application of opioid pharmacology in the setting of postoperative analgesia. Inappropriate doses, routes of administration, and dosing intervals and the concomitant administration of other sedatives often contribute to inadequate pain relief.1 Unlike most medications, analgesic administration occurs in a setting in which the patient can actually identify when additional medication is needed. Thus, if a xed dose schedule is to be applied, some exibility for supplementation and adjustments for individual variation must be included. Strategies that optimize the delivery of pain medication include using patient-controlled analgesia and allowing for supplemental or breakthrough doses of a rapid-onset analgesic. To be effective, frequent patient assessments must be undertaken. Simply asking a patient whether he or she has pain is not adequate. Directed questions should focus on the location of the pain; the severity of the pain, using a 0 to 10 scale; and activities associated with the pain, such as deep breathing, coughing, and ambulation. Most patients do not experience severe pain while lying still in bed, but once they begin to participate in their rehabilitation activity, pain becomes much more intense.

Opioid Selection
Choosing an opioid is a relatively simple process for the majority of postoperative pain patients. All of the opioids share a common mechanism of action and spectrum of side effects. For any given patient, one opioid may be better tolerated as determined from the medical history and is usually the best choice. Individual differences affecting drug distribution, metabolism, and elimination

may also affect the patients satisfaction with a given opioid. The following examples of these differences are illustrative. Morphine continues to be regarded as the gold standard for comparison among the opioids. Morphine has the advantage of being available in a wide range of dose forms, allowing administration via the oral, rectal, parenteral, and intraspinal routes. Unfortunately, morphine suffers from several disadvantages, making it a less than ideal analgesic. Morphine is poorly lipid soluble, which translates into a slow equilibration into the central nervous system. Following intravenous delivery, morphine has a relatively slow onset of action when compared with analgesics such as fentanyl, meperidine, and sufentanil. Administering an opioid as a component of the anesthetic (having anticipated the need for pain medication) and prescribing the drug on a xed schedule during the postoperative phase can usually overcome this disadvantage. Another disadvantage of morphine is its relatively short duration of action, typically in the range of 2 to 4 hours following a parenteral dose. With repeated doses, an active metabolite, morphine-6-glucuronide, accumulates, providing some increased duration of analgesia. Another important metabolite, morphine-3-glucuronide, may also accumulate particularly in the patient with renal failure. This metabolite may contribute to excitation of the central nervous system, producing myoclonus and possibly seizures. Metabolite accumulation is more pronounced with high doses, oral administration, and renal impairment. Meperidine continues to be used widely as a parenteral analgesic, despite several disadvantages. Meperidine is a synthetic compound, a phenylpiperidine, in the same structural class as fentanyl. It has the advantage of greater lipid solubility, allowing rapid transit across the bloodbrain barrier. This rapid onset of action tends to reinforce its use, particularly among many chronic pain patients. Meperidine is a very effective analgesic; however, it is seldom delivered at an appropriate dosage or interval. Parenteral doses of 75 to 100 mg are often inadequate for many patients.1 Furthermore, meperidine suffers from a short duration of analgesia, on the order of 3 hours, and is metabolized into a neuroexcitatory metabolite, normeperidine.19 Normeperidine tends to accumulate rapidly in renal failure or during therapy at high doses. Delivery of meperidine at doses exceeding 1000 mg/24-hour period can lead to seizures even in the absence of renal impairment. Considering the toxicity issues that limit dose escalation, meperidine has become relegated to a secondline drug status. Oral meperidine is a relatively ineffective analgesic. Only one fth of the oral dose is absorbed into the central circulation. Meperidine is a relatively impotent analgesic, requiring a dose of 500 mg to equal the parenteral dose of 100 mg. There is often a tendency to underdose patients, delivering small doses of 50 to 100 mg, which are equivalent to only 10 to 20 mg of parenteral meperidine. Hydromorphone is a morphine analogue, which has several decided advantages over morphine and meperidine. The chemical properties of hydromorphone provide for greater lipid solubility and a more rapid onset of action. Hydromorphone is approximately ve times more potent than morphine and may be administered via the oral,

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SECTION I General Principles

parenteral, epidural, and rectal routes. It is less predisposed to the accumulation of active metabolites and carries a much lower risk of neuroexcitatory effects. Oral hydromorphone is also poorly absorbed. Equivalent oral doses of hydromorphone are ve times the parenteral dose. The duration of action resembles that of most of the other opioids, at about 3 hours, requiring frequent dosing. A sustained release form of hydromorphone is now available, allowing more convenient dosing. Although there are many other opioids, fentanyl deserves mention as a common perioperative analgesicanesthetic. Fentanyl is approximately 50 to 100 times as potent as morphine. It is administered in microgram quantities and provides a very rapid onset of action following intravenous delivery. The lipophilic properties of fentanyl are responsible for its rapid onset and relatively short duration of action due to rapid redistribution. The half-life of fentanyl closely resembles that of morphine and meperidine, but in small-to-moderate doses it is rapidly redistributed into peripheral tissues, negating its central effects. Fentanyl has been used as a postoperative analgesic, but its major use has been as a transdermal patch for chronic and cancer pain. The transdermal patch is a useful means of delivery because it only needs to be applied every 72 hours.9 However, it can be difcult to titrate, is often poorly adherent, and is relatively expensive. The difculty in adjusting the dose to the individual has led to the recommendation that it not be used for postoperative pain. Fentanyl is not available as an oral tablet, but a transmucosal rapid release system is available and can be used as a rapid-onset medication for breakthrough pain.31

opioid preparations are available to allow for more convenient dosing intervals. INTRAVENOUS PATIENT-CONTROLLED ANALGESIA Pain is dened by the International Association for the Study of Pain as a sensory and emotional experience associated with tissue injury or described in terms of tissue damage or injury.28 Pain is always a subjective experience and can only be accurately assessed by the patient. Nurses and physicians are capable of recognizing many of the signs and symptoms of uncontrolled pain; however, their assessments are frequently inaccurate and tend to underestimate the patients reported pain score. Objective measures, such as heart rate, blood pressure, posture, and ventilatory pattern are rather insensitive measures and may be distorted by physiologic changes accompanying injury and drug therapy. With this perspective, it becomes obvious that the best person to regulate analgesic therapy is the patient. Patient-controlled analgesia (PCA) allows the patient to titrate small doses of intravenous, epidural, or subcutaneous opioid to regulate pain.47 The delivery of frequent small doses of analgesic allows the patient to maintain the blood opioid concentration close to his or her own minimum effective analgesic concentration. This approach minimizes wide swings in blood opioid levels, possibly reducing the unwanted side effects by preventing the wide swings associated with oral and parenteral opioid administration. At least theoretically, PCA reduces the potential for overdosage, because the patient will become too sedate to activate the device. In some circumstances, this margin of safety has been impaired by an overzealous spouse who depressed the PCA button to help the patient avoid pain while sleeping or by the rare patient who sought to maintain a state of postoperative oblivion and depressed the button every time he or she was awakened by the low saturation alarm on the pulse oximeter. Typical starting doses and intervals are listed for commonly used opioids in Tables 72 and 73. In many patients using PCA, a continuous opioid infusion in addition to the PCA may prove benecial. However, there is evidence to suggest that a continuous opioid infusion rate does not appear to improve analgesia in postoperative pain patients and that the PCA bolus only may work best. Continuous infusion rates may contribute to opioidrelated adverse events, such as respiratory depression, and do not appear to improve global pain scores.10, 29 Continuous delivery rates may be initiated at a basal level, as indicated in Table 73. In patients with a history of extended preoperative opioid use, such as those who have chronic cancer pain or who are on methadone maintenance, a continuous infusion rate should be initiated at a rate to deliver the patients preoperative opioid dose over a 24-hour period. The PCA mode dose should also be started at a higher dose to account for the patients opioid tolerance. In all cases, frequent reevaluation is necessary. Opioid dose requirements and pharmacokinetics vary considerably among patients, depending on age, sex, weight, medical condition, and prior opioid exposure. If set up inappropriately, a patient receiving PCA may spend hours watching the clock until time to administer the next PCA dose, never quite catching up with the pain.

Opioid Delivery
As discussed, there are numerous opioids available for clinical use. Similarly, there are many different routes by which to deliver these opioid preparations. Each route or delivery method is available to the trauma patient; however, depending on the patients overall condition, certain delivery approaches may be more advantageous. ORAL OPIOIDS Oral opioid selection can be confusing because of the large and ever-increasing number of opioid combination products. Predominant selections vary by region, but hydrocodone and oxycodone preparations are among the most commonly prescribed. Most of the opioids share a similar spectrum of duration, side effects, and efcacy, when delivered in equipotent doses. Dosing intervals and toxicity are more often related to the nonopioid analgesics, such as acetaminophen, aspirin, and ibuprofen, that are delivered in conjunction with the opioid. Morphine, meperidine, oxycodone, hydromorphone, and codeine all provide a duration of action approaching 3 to 4 hours. For many patients, an every 3-hour dosing interval is appropriate; however, with opioid-nonopioid combination tablets, this short interval could lead to excessive acetaminophen or aspirin delivery. Opioid-only preparations are now available for morphine, oxycodone, meperidine hydromorphone, and codeine. In addition, several sustained-release

Copyright 2003 Elsevier Science (USA). All rights reserved.

CHAPTER 7 Pain Management following Traumatic Injury TABLE 72

153

Common Opioid Analgesic Conversions

Agent Morphine Oxycodone Meperidine Methadone Fentanyl Hydromorphone Intramuscular 10 na* 100 10 0.1 1.5

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Intramuscular/Oral Ratio 1;3 1;2 1;5 1;2 na 1;5 Half-life (hr) 23.5 26 34 15120 13 24 Duration of Analgesia (hr) 36 24 34 48 13 24

*Oxycodone is not available in an injectable form. Methadone is available for intravenous delivery, but subcutaneous and intramuscular injections may cause local tissue injury. Intravenous methadone is roughly equivalent to morphine, except that its half-life is substantially longer and can accumulate with repeated doses. Fentanyl is not available in a tablet form; however, there is a transbuccal form.

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Parameters should be included to allow the nursing staff to increase the PCA bolus dose and to provide supplemental opioid doses if necessary. Also, postoperative nausea and vomiting may be more noticeable in patients receiving PCA opioids. Historically, many physicians prescribed a combination of an opioid with promethazine (Phenergan) or hydroxyzine (Vistaril). These agents offer little advantage with respect to pain control but can serve as effective antinausea therapy. Provision for possible nausea and vomiting can be made in the form of an as-needed dose of an antiemetic. This avoids the unnecessary delivery of medications that may provide little benet to the majority of patients and may reduce side effects such as somnolence. SPINAL OPIOIDS It can now be appreciated that opioids have produced analgesia by activating specic receptors found in peripheral nerves, the afferent spinal nerves in the dorsal horn, and at several sites in the brain. Selective targeting of peripheral opioid receptors has been shown to be modestly effective in ameliorating postoperative pain following arthroscopy surgery.39 A more effective means of selective opioid delivery has been the use of intrathecal and epidural opioids.20, 24 The potential advantages of targeting the spinal cord opioid receptors include good analgesia and less sedation, fatigue, dry mouth, and dizziness. This is accomplished by delivering the opioid directly into the vicinity of the target receptor, bypassing the systemic circulation. This translates into a sevenfold to 10-fold reduction with epidural administration and a 100-fold reduction in total morphine exposure with

intrathecal delivery, hence the reduction in systemic opioid side effects. A variety of different opioids have been delivered into the intrathecal and epidural spaces. In contrast to intravenous delivery, lipophilic agents are less attractive as spinal analgesics. The hydrophilic opioids, such as morphine and hydromorphone, appear better suited to epidural delivery because they tend to egress more slowly out of the subarachnoid space and allow for a greater duration and distribution within the central neuraxis. Lipophilic opioids, such as fentanyl, provide a more rapid onset of analgesia, but the duration of effect is relatively short. Continuous epidural infusion of fentanyl allows for more sustained analgesia; however, after the initial 10 to 24 hours, plasma fentanyl levels begin to approach those seen with intravenous fentanyl infusions, minimizing any potential selective spinal advantage. Spinal opioids are quite useful in managing the pain associated with chest wall trauma, thoracotomy pain, vascular injuries, and upper abdominal surgery pain. In these situations there is evidence to suggest that epidural analgesia may contribute to improved outcome and even improved survival.52 Combination therapy with an opioid analgesic, primarily morphine and hydromorphone, coupled with a local anesthetic can provide excellent analgesia allowing a further reduction in opioid requirement. Patient-controlled epidural analgesia is also available, which improves the exibility of delivery and allows for better tailoring of the analgesia to the patients needs. Spinal opioid delivery can reduce some opioid side effects, specically dry mouth, sedation, fatigue, and dizziness.20 Other opioid side effects, such as nausea, vomiting, constipation, urinary retention, and pruritus, do

TABLE 73

Suggested Starting Doses for Intravenous Patient-Controlled Opioid Analgesia

Agent Morphine Meperidine Hydromorphone Fentanyl* Concentration (mg/mL) 1 10 0.20.5 50 g/mL PCA Dose (mg) 1.0 10 0.2 1050 g

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Lockout (min) 68 68 68 68 Loading Dose (mg/kg) 0.1 1.0 0.015 13 g/kg

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*Fentanyl is an order of magnitude more potent than the other opioids and the dose is administered in micrograms.

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SECTION I General Principles

not appear to differ depending on the delivery route. Epidural hematoma formation and nerve compression are unique to spinal opioid delivery and can accompany the placement of an epidural catheter. This is a rare complication, usually associated with an underlying coagulopathy or concomitant administration of warfarin, heparin, or enoxaparin. Epidural or spinal analgesia should not be used in patients at risk for bleeding. Epidural catheter removal should take place only after correction of any coagulopathy or discontinuation of the anticoagulant. The most feared complication associated with opioid therapyrespiratory depressioninitially presented great concern among patients receiving spinal analgesia. This arose from the unexpected nding of respiratory depression developing in patients 6 to 20 hours after receiving a single dose of epidural morphine. The mechanism of this delayed respiratory depression involves the gradual diffusion of morphine through the spinal axis up to the respiratory centers of the medulla. Risk factors for respiratory depression include delivery of opioids in the thoracic or cervical epidural space, opioid nave individu als, and concomitant systemic opioid delivery. As more experience has developed with the use of spinal opioids, the risk of respiratory depression has diminished and at present is not thought to exceed that seen with other routes of opioid delivery.

Pain Treatment in the Opioid-Tolerant Individual

Preexisting opioid use, in the form of protracted consumption of opioid analgesics following trauma, or a history of substance abuse is not an uncommon nding among orthopaedic trauma patients. Staged surgical procedures to repair multiple injuries will result in the need for and the development of a tolerance to the opioids as indicated by escalating demands. Individuals with a history of opioid abuse are particularly difcult to treat in this setting. Conicting issues make it very difcult to sort out appropriate demands for pain treatment from drugseeking behavior. Unfortunately, there is no simple solution to this problem; however, several generalizations can be made to guide analgesic therapy in these patients. Patients with a history of prior opiate exposure, illicit or therapeutic, require greater doses of opioid than the opiate nave population. The degree and duration of the opioid exposure determines the amount of tolerance. Therefore, do not prescribe the usual outpatient opioid regimen because it will not be adequate. Patients with a history of opiate abuse, cancer pain, or chronic pain need higher than usual doses. Failure to provide adequate analgesia will generate appropriate complaining, requests for more medication, and overt pain behavior and hostility. This behavioral pattern has been labeled as pseudoaddiction.46 It can be characterized as a circumstance in which the patients behavior mimics the drug-seeking behavior commonly attributed to opioid abusers but in fact represents an appropriate response; it typically abates with adequate pain control. A general rule of thumb in treating

this population is to provide 50% to 100% more opioid than the patient was taking during the preoperative period. This may be accomplished by converting the patients usual preoperative opioid dose into morphine or oxycodone equivalents per 24-hour period, add to this preoperative dose an additional 50%, and deliver it as a continuous intravenous infusion or as a long-acting oral dose form. Be careful to factor the route of delivery into the conversion. Remember, only one half to one fth of the oral dose reaches the central circulation. An additional 50% of the preoperative (24 hour) daily dose should be factored in and be provided in small as-needed doses for breakthrough pain. One of the greatest challenges in treating the opioidtolerant population is determining how and when to begin withdrawing opioid therapy. In the majority of patients, withdrawal occurs without specic intervention, because most patients taper themselves off as their pain resolves. This process may be slower in the opioid-tolerant individual or nonexistent in the patient with a history of substance abuse. Issues of chronic pain, protracted disability, and tolerance to the opioids may further complicate the picture. Experience in treating the opioidnave population can be used to determine a strategy to wean the tolerant patient off opioids, namely, by doubling the usual recovery phase. Expect the opioid-tolerant patient to require an extended period of analgesic use and to have pain persist for longer than usual. Opioid tapering can begin on a gradual basis. A key point is to avoid becoming frustrated with the resistant patient. Formulation of a treatment plan and adherence to the taper schedule with calm insistence usually achieves the desired goal. Opioid access can also be used as a motivational aide to promote participation in the rehabilitation program. It is also important to use adjuvant medications, such as NSAIDs and tricyclic antidepressants. These agents are often overlooked, but they can provide signicant pain relief and offer supplemental benets that include improved sleep. An evening dose of nortriptyline, amitriptyline, or doxepin can help obviate the need for a hypnotic at bedtime and may offer some supplemental analgesia. The NSAID can be added on a regular dosing interval around the clock for a 5- to 7-day period and then be reevaluated.

ADJUVANT ANALGESICS

zzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzz Traumatic injuries frequently involve direct injury to neural elements, including the brain, spinal cord, and peripheral nerves. Neuropathic pain often responds poorly to the analgesics used in the treatment of pain arising from bone or tissue trauma (nociceptive pain). Examples of neuropathic pain states include phantom limb pain; neuritis-neuralgia; complex regional pain syndrome, type I (reex sympathetic dystrophy) and type II (causalgia); and spinal cord injury pain. Opioids may be partially effective in relieving neuropathic pain; however, neuropathic pain states are often refractory to conventional opioid doses. Nonopioid analgesics, often referred to as adjuvant analgesics, include the tricyclic antidepressant, anticonvul-

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sant, and antiarrhythmic drug classes and are often benecial in treating neuropathic pain.

Tricyclic Antidepressants
Classically, the tricyclic antidepressants, amitriptyline in particular, have been widely used to treat neuropathic pain. These compounds have several possible sites of action in the nervous system. Amitriptyline, nortriptyline, and desipramine block the reuptake of norepinephrine and serotonin into the presynaptic neuron. The norepinephrine pathways are intimately involved with regulating the liberation of enkephalin within the spinal cord. Presumably, the tricyclic antidepressants enhance enkephalins release, producing analgesia. Other benecial effects include direct inhibitory effects of the NMDA receptor, reducing the excitatory effects of glutamate on the wide-dynamic range neuron, and anticholinergic effects responsible for producing sedation. When administered for pain treatment, the tricyclic antidepressants need only be administered as a single dose at bedtime. This reduces the impact of the sedative effects during the day, facilitates sleep, and improves patient compliance. As indicated in Table 74, these compounds exhibit a long half-life; thus, more frequent delivery is unnecessary. Although amitriptyline has been the most commonly used agent in this class, nortriptyline may be the better choice. Nortriptyline produces fewer anticholinergic effects. This translates into less daytime sedation and better patient tolerance. It is important to start slowly with these drugs, particularly in the elderly, escalating the dose at 1- to 2-week intervals. Side effects common to all of these compounds include weight gain, dry mouth, orthostatic hypotension, urinary retention, and cardiac arrhythmias.

Anticonvulsants
Anticonvulsants are becoming increasingly used in the management of neuropathic pain. The availability of several new compounds that do not appear to share the bone marrow depression and hepatotoxic effects linked to the older anticonvulsants, such as carbamazepine, pheny-

toin, and valproic acid, has resulted in less risk and greater patient acceptance. Gabapentin has become the rst choice of many pain treatment specialists.2, 27, 34 Gabapentin is a novel anticonvulsant that is not metabolized, is relatively devoid of serious toxicity, and can be dramatically helpful in 20% of patients suffering from neuropathic pain. Although relatively nontoxic, gabapentin is not devoid of side effects. Approximately 20% of patients treated with gabapentin experience treatment-limiting side effects such as sedation, fatigue, and dizziness.2, 34 For many elderly patients, slow escalation, beginning with an evening dose, helps to reduce the impact of these side effects and improves patient acceptance. Most patients realize improvement at doses ranging between 900 and 2400 mg/day. The relatively short half-life requires dosing intervals of 6 to 8 hours. Topiramate is another compound that has a potential role in treating neuropathic pain. Experience with topiramate is limited to anecdotal reports, but these are encouraging. Unfortunately, topiramate produces considerable sedation in many patients and may contribute to renal stone formation owing to its weak carbonic anhydrase inhibition. Carbamazepine continues to be the gold standard for neuropathic pain treatment. It is the only anticonvulsant approved for this specic indication by the Food and Drug Administration. Unfortunately, carbamazepine has numerous disadvantages that include the need to monitor the results of blood cell counts and liver function tests, frequent gastrointestinal and dermatologic side effects, and the potential for aplastic anemia. Carbamazepine, phenytoin, and valproic acid all carry a similar potential for bone marrow and liver damage. Valproic acid also carries a 1:200 risk of causing pancreatitis. Careful patient counseling and regular monitoring must be undertaken when prescribing these agents. Despite their adverse potential, the anticonvulsants may prove uniquely effective in managing neuropathic pain.

Neural Blockade
Another approach to the management of painful injuries is through the direct blockade of afferent neuronal transmission using local anesthetics. Regional anesthesia may be

TABLE 74

Adjuvant Analgesics
Agent ANTICONVULSANTS Gabapentin Topiramate Carbamazepine Valproate Phenytoin ANTIDEPRESSANTS Nortriptyline Amitriptyline Desipramine

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Dose (mg) Target Dose Range (mg) Dosing Interval (hr) Half-life (hr)

100300 25200 100200 250 100 25100 25100 25100

9002400 200400 6001200 5001000 300 50100 50150 50150

68 12 8 8 8 24 24 24

6 21 15 1012 22 31 15 18

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SECTION I General Principles

used alone or in combination with general anesthesia to provide perioperative analgesia for patients undergoing surgical repair.23 Regional anesthesia offers several advantages over general anesthesia that can favorably affect surgical outcome.23, 42, 52 Benecial effects include complete pain blockade; prevention of central nervous system sensitization; and a sympathectomy, which may improve circulation.7, 50 The benets of regional anesthesia are particularly notable in high-risk patients suffering from advanced medical ailments and in the frail elderly population.52 Additional benets of neural blockade can include extended analgesia into the postoperative period, less opioid requirement, and an associated reduction of opioid-related side effects. Neural blockade for postoperative analgesia can be divided into two types: long-acting single injection nerve blocks and continuous techniques using an indwelling catheter. Long-acting local anestheticsbupivacaine, etidocaine, tetracaine, and ropivacainecan be used during the perioperative period to provide prolonged anesthesiaanalgesia for 6 to 10 hours from initiation. The addition of epinephrine or clonidine extends the duration of most local anesthetics. Clonidine may be particularly helpful in the pediatric patient because it does not carry as much risk of hypotension or bradycardia as that commonly encountered when it is used in the adult population. Clonidine and other -agonists may provide supplemental analgesia and prolongation of nerve blocks without introducing the tachycardia and anxiety experienced with epinephrine. Typical settings in which long-acting blocks may be helpful include brachial plexus block for shoulder surgery, femoral nerve block for knee reconstruction, and ankle blocks for foot surgery. The advantages of prolonged neural blockade include faster discharge from the postanesthesia care unit; less pain in the early postoperative period; and lower risk of opioid side effects such as nausea, vomiting, and urinary retention. There is also a body of evidence that indicates early intervention with regional anesthesia, before incision, may reduce the intensity of postoperative pain even 7 to 10 days after surgery. Disadvantages of long-acting anesthesia include limited use of the extremity, potential for nerve or tissue damage secondary to unrecognized nerve compression because of a lack of sensation, and severe pain developing at home when the block resolves on the evening of surgery. The last issue can be a signicant problem because the block analgesia may wear off abruptly and the patient may not realize what is happening. The patient or the family may then make many anxious calls to the on-call surgeon, fearing that something is going wrong. It is also difcult to achieve pain control if inadequate analgesics have been prescribed. Successful use of longacting anesthetic nerve blocks in an outpatient orthopaedic practice is dependent on careful patient education regarding what to expect, emphasis on taking the opioid analgesics in anticipation of the block wearing down, and ensuring that the patient has sufcient analgesic medication available. Special care must also be taken by the patient to avoid pressure injuries, such as ulnar or common peroneal nerve injuries.18 These two nerves are particularly susceptible to compression during the postoperative period when brachial plexus or epidural anesthetics are administered. Both

the patient and the caretakers should be counseled before surgery about the potential risks and the need for soft padding around the anesthetized region. This counseling should be repeated again before release from the recovery area. Regional anesthesia of the brachial plexus can be accomplished via several different techniques. The interscalene nerve block is extremely useful in providing anesthesia and analgesia for shoulder and upper arm procedures.44 Successful anesthesia is usually accomplished by delivering a volume of 20 to 40 mL of local anesthetic into the interscalene groove at the C-6 level. Using an insulated needle with a nerve stimulator can facilitate the identication of the appropriate injection site. Good anesthetic coverage can be obtained over most of the shoulder and upper arm; however, coverage around and below the elbow is often variable. This technique is most useful for shoulder and upper arm procedures. Postoperative analgesia may persist up to 10 to 12 hours following the initial nerve block. Disadvantages of interscalene blocks include the development of Horners syndrome, hoarseness, risk of a pneumothorax, epidural anesthesia, and accidental spinal injection; in addition, almost every patient experiences diaphragmatic dysfunction.45 Inhibition of the phrenic nerve commonly accompanies the interscalene nerve block and can lead to a sense of dyspnea, causing anxiety. Rarely does a patient experience signicant respiratory embarrassment. A continuous interscalene block may be performed using several techniques. One method involves the use of a 20- to 16-gauge intravenous catheter to perform the block, which can be sutured or taped into position for repeated injections or a constant infusion. Several commercial systems have become available for continuous nerve blocks. One system uses a modied epidural needle and catheter. The needle is insulated and can be used in conjunction with a neurostimulator and may allow better positioning of the catheter. Other approaches to the brachial plexus include the supraclavicular, infraclavicular, and axillary techniques. The supraclavicular technique provides access to the plexus at the level of the cords, where the neural structures are the most tightly associated, allowing the delivery of smaller anesthetic volumes. This advantage may be offset by a greater potential for a pneumothorax because the plexus is adjacent to the pleura. The infraclavicular approach may provide a more stable method of securing a continuous catheter. The axillary approach is often the easiest and is very useful in providing anesthesia below the level of the elbow. Lumbar plexus blocks can be performed using an inguinal approach or paravertebral blocks. These locations provide excellent coverage of the anterior thigh and can be at least partially helpful in providing acute perioperative pain relief for knee reconstruction surgery. As with brachial plexus blocks, a continuous catheter may be inserted for repeated injection or for a continuous infusion. Combined lumbar plexussciatic nerve blocks can be used to provide broader coverage of the entire leg. Unfortunately, the amount of anesthetic required to block both regions often approaches the toxic limits for local anesthetics. The advantage of these techniques is that they allow the

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affected extremity to be isolated, unlike epidural anesthesia, which typically covers both limbs. This allows the patient to ambulate with the assistance of crutches unaided, as the motor function remains intact in the nonoperative limb. Directed postoperative delivery of local anesthetic can also be accomplished by inserting a continuous catheter, such as an epidural catheter, into the subcutaneous tissue adjacent to a supercial nerve or incision. Continuous or periodic delivery of local anesthetic into sites such as an amputation stump or an iliac crest bone harvest site have been reported to be helpful in controlling postoperative pain and reducing opioid requirement. Several disposable commercial products are now available that include a catheter linked to an auto-infuser device, usually a Silastic or latex balloon reservoir. A ow-regulator provides a near constant delivery of local anesthetic, depending on the reservoir capacity, over hours to days.

EPIDURAL ANALGESIA

zzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzz Epidural analgesia with local anesthetics gained its initial popularity in the management of labor pain during childbirth. With the discovery of the opioid receptors came the recognition that morphine could be delivered into the intrathecal or epidural spaces to selectively target the spinal opiate receptors to provide excellent analgesia without the large systemic doses needed for intravenous or intramuscular analgesia. In some respects, spinal opioid delivery has not quite lived up to expectations, in part because most opioid side effects are related to the binding of the opioids to receptors located primarily within the central nervous system. Thus, opioid side effects, such as nausea, vomiting, and constipation, have not been reduced with spinal administration. Other side effects, including urinary retention and pruritus, may be more problematic. The one key benet of intrathecal opioids has been reduced sedation. There may also be some advantages to combining intraspinal opioids with one or more alternative analgesics, such as a local anesthetic, clonidine, and possibly a NSAID, in that these combinations can produce a synergistic effect, reducing individual toxicity and improving analgesia. Epidural anesthesia and analgesia are most frequently delivered into the lower lumbar region. This is effective for providing anesthetic coverage of the lower extremity and abdomen. If sufcient volume of anesthetic is delivered, anesthetic levels may reach the entire thoracic region and extend to the cervical levels. Coverage of the thoracic region, for example, to provide analgesia for a thoracotomy, can be accomplished easily with lumbar epidural morphine delivery. Morphine tends to distribute rather widely within the intrathecal space and spreads well into the thoracic region. However, when using continuous local anesthetic infusions for postoperative analgesia, the anesthetics do not spread very far within the neuraxis unless driven by sheer volume. Thus, continuous local anesthetic epidural infusions tend to accumulate in the region about the catheter, often creating an area of dense anesthesia, producing a numb and weak limb. For abdominal or

thoracic surgery, this presents little problem if the catheter tip is placed at the appropriate dermatomal level, that is, a thoracic epidural. Most patients rarely notice sensory impairment over the chest or abdomen. However, weakness and the absence of sensation in the nonoperative limb are frequently a source of annoyance to most patients. Diminished sensation may contribute to nerve compression injuries, heel erosion, and bedsores. The tendency of local anesthetics to show limited spread within the epidural space can at times be exploited to provide focal anesthesia. By directing an epidural catheter laterally within the epidural compartment, it is possible to provide a unilateral anesthetic block. This is occasionally achieved inadvertently during catheter insertion, but the catheter may be positioned intentionally using an angulated paramedian approach. Fluoroscopic guidance is also helpful in steering the catheter into the lateral region adjacent to the targeted nerve roots. By infusing small volumes of local anesthetic through the catheter, a persistent unilateral block may be obtained for days or even weeks. Buchheit and Crews have used cervical epidural infusions in the rehabilitation of complex regional pain syndromes of the upper extremity.3 Unilateral blockade was attained in their patients without evidence of respiratory embarrassment. Cervical epidural analgesia appears to offer greater catheter stability and may be used for extended periods.

SUMMARY

zzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzz In summary, multiple medications, routes, and techniques are available for pain control in the patient with multiple injuries. Optimal selection usually involves multimodal therapy. This allows for increased control with minimal side effects. In the same manner a patients pain control can be optimized even in the face of chronic illness or during the acute physiologic instability of the recently injured patient. Tailoring the analgesic approach to the patients medical condition, desires, and physical injuries ultimately produces the best outcome.
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