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Postoperative Pain Management Ray H. d'Amours, MD' F. Michael Ferrante, MD, FABPM

* Distressing postoperative pain remains a prevalent problem. Poorly treated pain contributes to patient suffering and may prevent rapid recovery and rehabilitation. An understanding and application of the basic principles of pain management can provide adequate analgesia for the majority of postoperative patients. More advanced methods of pain control can allow excellent relief for virtually all patients but may require the presence of a dedicated pain management service. This article reviews the principles and practice of modern postoperative pain management.

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Key Words: postoperative pain, nonsteroidal anti-inflammatory drugs (NSAIDsl, opioids Rav H. d'Amours

F. Michael Ferrante

D

espite great advances in medicine over the past few decades, numerous studies have shown that distressing postoperati1.c pain remains a prevalent problem ( 16). Effective multimodal pain treatment regimens have been developed that can provide relief of postoperative pain for the vast majority of patients. Some of these techniques require expensive technology, intensive patient surveillance, or a dedicated acute pain service and may therefore be unavailable to many patients. Even without these techniques, postoperative pain management can be improved through an understanding and application of basic pain management principles. The treatment of postoperative pain is in keeping with the physician's primary goal of relieving unnecessav suffering. Elimination of nociceptive signals to the central nervous system may also serve to blunt autonomic, somatic, and endocrine reflexes with a resultant decrease in perioperative morbidity. By facilitating postoperative physical therapy and rehabilitation, effective postoperative pain management may permit faster recovery, decrease cost, and JOSPT Volume 24 Number 4 October 1W6

'

Assistant Professor of Anesthesiology; Director, Acute Pain Service, Department of Anesthesia, University of Pennsylvania Health System, 3400 Spmce Street, 1102 Penn Tower, Philadelphia, PA 19104 Associate Professor of Anesthesiology and Medicine; Director, Anesthesia Pain Management Program; Director, Cancer Pain and Symptom Management Program, University of Pennsylvania Health System, Philadelphia, PA

allow better use of scarce health care resources (31) .

ANATOMY AND PHYSIOLOGY Pain is defined as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage" (35). Painful stimuli are transmitted to the central nervous system (CNS) where they are experienced as pain by a process called nociception. Nociception begins in the periphery with transduction, whereby noxious stimuli are converted into electrical activity by peripheral nerves (nociceptors) . The responsiveness of nociceptors can be increased by the local release of numerous substances (eg., prostaglandins, bradykinin, and histamine) associated with tissue injury (4,241. The nociceptive electrochemical impulses are first carried to the spinal cord by primary afferent fibers (unmyelinated type C and thinly myelinated A-delta fibers). The grey matter of the spinal cord has a laminated cytoarchitectural structure re-

ferred to as Rexed's laminae (44). The primary nociceptive afferents synapse with modulatory interneurons in the dorsal horn of the spinal cord, primary in laminae I, 11, and V (29,30). At this point, the signals can be modulated by intrinsic inhibitory pathways. Descending inhibitory fibers originating in the higher brain centers release various neurotransmitters, including norepinephrine, serotonin, and enkephalins (5,17,46,58), which modulate the flow of the afferent impulses. These inhibitory tracts can be activated by endogenous opioids or other neurotransmitters (64) and serve as an intrinsic analgesic system. Similarly, stimulation of larger myelinated sensory fibers in the periphery close to the noxious stimulus (as with rubbing the painful area) will inhibit nociceptive transmission in the spinal cord (34.60). Stimulation of these large myelinated sensory fibers is thought to be the mechanism by which transcutaneous electrical nerve stimulation (TENS) provides pain relief. From the dorsal horn, nocicep tive transmission is carried rostrally through projection neurons. These 227

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PERCEPTION

Cortex

Epidural opioids Suborochnoid opioids

f

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Tholomocorticolproject ions

I

MODULATION

Epidural

Tholornus A

FIGURE 1. The nociceptive pathways. Each step in the process offers opportunity for intervention to block or mod;@ nociceptive transmission. (Reprintedfrom Ferrante FM, VadeBoncouer TR: Postoperative Pain Management, New York: Churchill Livingstone, 1993, with permission).

neurons travel as part of the spinothalamic and spinoreticular tracts to eventually synapse in variorls rostra1 centers, including the thalamus, reticular activating system, limbic system, and cortex. In these areas, the nociceptiw input is integrated with emotional and affective components of pain through the process of p e r c e p tion. In response to intense o r repeated stimulation, the neural pathways that transmit nociceptive impr~lscsundergo structural and physiologic changes. After such stimuli, the neurons mediating nocicep tion in the dorsal horn show dramatic increases in the frequencv of discharge with an accompanying increase in the perception of pain (42, 63). This process is termed central hypersensitization o r wind-up. If the nociceptive pathways are pharmacologically blocked before intense stimulation occurs. these changes are prevented o r minimized. T h e clinical application of this technique, in which analgesic interventions are instituted before a surgical procedure k g i n s to prevent development of wind-up, is termed preemptive anal-

gesia. I.ocal anesthetic blockade, along with opioids and "Gmethvl-Daspartate antagonist drugs such as ketamine, all have been shown to decrease wind-up when given before tissue trauma occrlrs ( 1 0.14.58). T h e clinical significance of preemptive analgesia remains uncertain but may contribr~teto reductions in postoperative pain and the possible develop ment of chronic pain syndromes. T h e various techniques of postoperative pain management are designed to modify o r interrupt nociceptive pathways along their course from periphey to brain (Figure 1). I.ocal anesthetics in.jected into the periphey, nerve plexi, epidural, o r subarachnoid space will block nociceptive transmission. Because the small nociceptive fibers are particularly sensitive to dilute concentrations of local anesthetic, it is sometimes p o s sible to selectively block these fibers while sparing those which mediate other sensoy and motor modalities (21) . Nonsteroidal anti-inflammatory drugs (NStUDs) block production of prostaglandins that sensitize peripheral nociceptors after tissue injury. In the spinal cord, the intrinsic analgesic svs

tems can he activated bv transcutme011selectrical nerve stimulation or bv application of opioids or other inhibitory neurotransmitters to their corresponding receptors on the 1:ociceptive fibers (5). Administration of these drugs directly into the epidural or s u h arachnoid space bypawes the bloodbrain barrier, which may increase both their efficacy and duration of action (26). Systemically administered opioids act at receptors throughout the central nervous .system to modulate the propagation of nociceptive impulses (24).

GENERAL PRINCIPLES Effective postoperative pain management begins preoperatively with the psychological preparation of the patient. T h e patient should be informed of what procedures will take place and what degree of pain can be expected. (Patients shorlld never be promised that thev will be completelv free of pain after an operation. Thev should not be promised anesthesia as this will promote rlnreasonahle expectations regarding their analgesia.) T h e methods for postoperative pain assessment and treatment should be

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explained. T h e patient should be encouraged to communicate any questions or concerns.

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There is tremendous interpatient variability in the dose of opioid required to control postoperative pain, even when doses are adjusted for weight. After an operation, the first step in providing postoperative analgesia is to ensure adequate assessment of the patient's pain. Postoperative pain is a dynamic phenomenon which changes rapidly in response to a variety of influences, including movement, dressing changes, and physical therapy. A dose of pain medicine which is appropriate in o n e instance may quickly become insufficient in another. The management of postoperative pain is predicated upon the need for frequent assessment and rapid response to changes in pain experienced by the patient.

NONSTEROIDAL ANTIINFLAMMATORY DRUGS (NSAIDS) Nonsteroidal anti-inflammato~ drugs inhibit peripheral pain and inflammation by blocking the action of the enzyme cyclo-oxygenase which converts arachidonic acid to prostaglandins (59). Evidence also exists that these drugs exert some central analgesic effect in the spinal cord (32). Their ability to block cvclo-oxvgenase also explains the common side effects associated with their use, including decreased platelet aggregation with prolongation of the bleeding time, gastrointestinal irritation o r bleeding, and decreased renal blood flow in dehydrated patients ( 1.40.48).

M'ith short-term administration in the postoperative period, these side effects are generally negligible. Clinically significant postoperative bleeding has not been associated with use of NSAlDs after several procedures (19,22.36,50,5.5). Nonsteroidal antiinflammatoy drugs may be contraindicated for use after some procedures which require meticulous hemostasis, where surgical hemostasis has not been achieved, or when other anticoagulants have been given. Patients who are severely dehydrated o r have significant renal dysfunction may not be candidates for NSAIDF (11). The only NSAID available for parenteral use in the United States is ketorolac. This NSAID has been shown to have a significant morphine-sparing effect (20) when given for postoperative pain. Like any NSAID, ketorolac is associated with a risk of gastrointestinal irritation and bleeding, particularly in elderly patients receiving high doses. The recommended dose is 15 mg intravenouslv every 6 hours with reduced doses for elderly patients, small patients, and those with renal dysfunction. Because of its frequent side effects and high cost, there is little reason to give ketorolac to patients who can take NSAIDs by mouth. Although not approved for use in children, substantial experience has already accumulated in that population (53).

Systemic administration of opioids remains the most commonly used technique for treatment of patients with moderate to severe postoperative pain. Many years of clinical use have established the safety and r~sefulnessof these drugs when p r o p erly administered. They provide analgesia by mimicking the effect of endogenous opioids at specific r e c e p tors in the central nenrous system (24). In sufficient doses, the potent opioids will relieve most types of post-

COMMENTARY

operative pain, generally with toleralde side efrects. The fact that many patients still experience distressing pain after their operations despite the widespread use of opioids is an indication that these drugs are not being used to their full potential. An understanding of the proper use of systemically administered opioids and an awareness of the factors which prevent such use can lead to iniproved relief of postoperative pain. A variety of opioids are available for treatment of postoperative pain. These drugs can be divided into two categories: opioid agonists and mixed opioid agonist/antagonists. The mixed agonist/antagonist drugs. which include nalbuphine and butorphanol, work simultaneously at diffcrent types of opioid receptors. They act as agonists at one receptor and as antagonists at another. These agents have a submaximal analgesic efkct compared with pure opioid analgesics (ceiling effect) and may antagoni7e the analgesia offered by pure agonists. Most of the commonly used opioid analgesics are pure agonists, including morphine, hydrornorphone, meperidine, and fentanyl. These drugs all work by stimulation of Mu opioid receptors throughout the central nenrous system. All can provide excellent analgesia and have the capacity to cause similar side cffects. The clinical differences in these drugs result primarily from individual pharmacodynamic and pharmacokinetic differences. The formation of active metabolites with certain opioids may restrict their use in some patients.

Morphine Morphine, which was originally isolated from the juice of the poppy plant by Sertrlrner in 1806, is the prototypical opioid. Morphine is characterized by its high degree of water salability, its intermediate duration of action, and by the presence of an active metabolite. M'ith rapid intravenous in.jection, morphine can

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cause release of histamine with resultant rash and vasodilation. Morphine is metabolized primarily in the liver with the metabolites excreted in the urine and bile. Morphine metabolism r e a ~ l t sin the formation of significant amounts of the active metabolite morphine-&gIucaronide which is excreted by the kidneys. Thus, morphine may he a poor choice for chronic administration in patients with decreased renal function (33). Morphine can also be given orally. T h e equivalent oral dose is three times the parenteral dose.

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Hydrornorphone Hydromorphone, a semisynthetic derivative of morphine, is about six times as potent as morphine when administered intravenously and is not thought to have any clinically significant active metabolites. Like morphine, hvdromorphone can also be given orally.

Fentanyl Fentanyl is a synthetic opioid which is 75 to 100 times as potent as morphine when administered intravenously for short periods. It has n o activc metabolites. Althol~ghthe elirninated half-life of fentanyl is at least as long as that of morphine, its duration of' analgesia is usually shorter, owing to its rapid redistribution from the plasma to other tissues after intrw.enous injection.

Meperidine Use of meperidine for postoperative pain is complicated by generation of the excitatory metabolite normeperidine. This compound is eliminated by the kidney hut can accumulate even in patients with normal renal function. In sr~fficient quantities, normeperidine may cause mvoclonus and seizures ( 2 ) . For this reason, use of meperidine is discouraged except for very brief periods. 230

Side Effects Concern about side effects is often cited as a reason for limiting the dose of opioids. These side effects incli~denausea, vomiting, and, most significantly, respiratory depression. Nausea and vomiting have been shown to occur in 2 5 4 0 % of patients and pruritus in 10% of patients receiving opioids for postoperative pain ( 15). Nausea, which can be worsened by residual anesthesia and bv the o p eration itself, can usually be effectively relieved with intravenous metoclopramide, prochlorperazine, or droperidol. Pruritus from svstemically administered opioids is seldom severe and rarely requires treatment. Respiratory depression is the side effect of most concern to clinicians and a reason why manv clinicians medicine they limit the dose of are willing to give. In sufficient doses. most opioid analgesics will cause lifethreatening respiratory depression. It should be remembered, however, that patients will rarely experience both significant pain and significant respiratory depression. In fact, o n e of the axioms of opioid analgesia is that side effects generally occrlr at plasma levels greater than those required for analgesia. Side efftms can, therefore, be best managed by carefully acljr~sting the administered dosc so that it is n o more than that required for analgesia. M'hen it occurs, significant respiratory depression is best treated with intravenous naloxone. T h e size of the dose should be tailored to the degree of respiratory depression. Severe respiratory depression o r apes may require treatment with doses of 0.4 mg o r more. Less serious cases may be treated with repeated doses of .04 mg o r less. Intravenous n.A loxone works very quickly: small doses given every minute can help avoid complete opioid reversal with resultant severe pain. It should be remembered that an intravenous dose of naloxone will last only about 30 minutes, while the effects of an opioid

overdose can last much longer. In cases of severe overdose o r when long-acting opioids have been used, additional doses of naloxone may he required. Intravenous naloxone infusions can also be used: the usual dose range is 1-5 pg/kg/hr.

Opioid Administration Fear of side effects shoi~ldnever cause o n e to limit the dose of opioid to some fixed arbitrary limit, as this will neither ensure prevention of side effects nor allow optimal analgesia for all patients. Some patients, particularly those who take opioids chronicallv, mav, require verv large doses of . opioids to achieve analgesia. There is tremendous interpatient variability in the dose of opioid required to control postoperative pain, even when doses are acljusted for weight (3). T h e variation in dose results from both pharmacokinetic and pharmacodvnamic factors (22.24). This great pharmacologic variabilitv mandates that we abandon anv notion of o n e "correct" dose of opioid for the control of postoperalive pain and that we he prepared to occasionally administer doses far less o r far greater than we would consider customary. T h e use of "routine" orders for analgesics. whereby a fixed dose of drug is administered usually by the intramuscr~larroute, is likely to fail for the majority of patients. Althor~gh convenient, it does not allow for rapid acijustment of plasma opioid concentrations to suit the needs of the patient at any instant. Intravenous administration of opioids is preferred over the intramuscular route whenever possible. Absorption of opioids from muscle is quite variable and may be slow, particularly in patients who are cold o r volume depleted. After intravenous in,jection, most opioids will reach near maximal effect within several minutes. T h e rapid onset allows quick assessment of the effectiveness of the administered dose. Additional doses can then be given promptly. \'olrlmc 24 Nrmber 4 October I!N6 *JOSFT

CI.INICAL

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Effective postoperative pain management begins with the psychological preparation of the patient. Relief of pain even for problematic patients can often be obtained simply by standing hv the bed and administering intravenous doses of morphine every 5 minutes. If no relief is o h tained with the first doses, subsequent doses should he increased by at least 50%. Administration of increasing doses should continue until either analgesia o r significant side effects result. If significant side effects d o occur, they should be treated. and additional opioid given as needed to control pain.

2. At any instant, there is a narrow range of morphine plasma concentrations which will allow effective analgesia without significant side effects. Exceeding this range will create more serious side effects; concentrations below this range will result in inadequate analgesia. Where this therapeutic range lies varies from patient to patient (22). Intravenous patientcontrolled analgesia allows more precise control of plasma concentrations with resultant improved analgesia and reduced side cffects. Figure 2 shows that predetermined intramuscular doses result in plasma morphine concentrations that are often above o r below the therapeutic range. This system depends on the participation of a nurse and on the uptake of drug from muscle and is therefore too slow to respond to the patient's needs. Intravenous patientcontrolled analgesia is associated with a high degree of patient satisfaction because it provides rapid adjustment of analgesic plasmil levels and because most patients er!jov maintain-

COMMENTARY

ing control over their own pain management. Microprocessorcontrolled patientcontrolFed analgesia pumps are now widely used for intravenous administration of opioids. Typically, one selects the dose of drug to be delivered to the patient on demand (the demand o r patientcontrolled analgesia dose) and the lockout interval, which specifies a mandatory waiting period between doses. Patientcontrolled analgesia therapy should be initiated with a loading dose of analgesic to quickly achieve pain relief. Most pumps will also allow the addition of a continuous background infusion of drug. Clinical studies (3.39) have shown that the majoritv of patients d o not benefit from the addition of a continuous infusion to their patientcontrolled analgesia regimen. Rather, for most patients, it results in greater quantity of drug used without improving analgesia (339). Some patients will benefit from addition of a continuous infusion, particlllarly those with a history of chronic opioid

PATIENT-CONTROLLED ANALGESIA T h e understanding that opioid doses must be individualized for each patient has led to the development of patientcontrolled analgesia. The term patientcontrolled analgesia describes not a device but rather a concept of analgesic administration where the patient self-administers doses of pain medicine as needed. Patientcontrolled analgesia use depends on the fact that the patient knows better than anyone when a dose of analgesic is needed. Ry selfadministering frequent small doses of analgesic, the patients can adjust for their own pharmacokinetic and pharmacodynamic i~niqi~eness to rapidly achieve and maintain effective plasma concentrations of opioid. This occurs even as the level of pain changes from moment to moment. The benefit of using patientcontrolled intravenous morphine compared with intermittent intramuscular closing of morphine is demonstrated in Figure

Intermittent intramuscular dosing

Intravenous on-demand dosing by

FIGURE 2. Plasma concentrations of opioid as a function of time when given bv intravenous patient-controlled analgesia (PCAJ or bv intermittent intramuscular injections. For each patient, there is a narrow range of plasma opioid concentrations which allows analgesia without serious side eriects. The minimum effective analgesic concentr'~tion(MEAC)is the concentration ofanalgesic in plasma required to provide satisfactory pain reliei. This value varies widelv behveen patients. lntermittent intramuscular injections provide plasma concentrations which are frequentlv above or below this range, resulting in sedation or poor analgesia. Intravenous patient controlledanalgesia allo~vsmore precise control of plasma opioid concentrations with improved analgesia and reduced side effects. (Reprinted from Ferrante FM, VadeBoncouer TR: Postoperative Pain Management, New York: Churchill Livingstone, 1993, with permission).

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use and high analgesic requirements. Some patients will find that addition of a continuous infusion improves their sleep by decreasing the number of times they must awaken to administer doses. It should be remembered though that with "demand onlv" patientcontrolled analgesia use, the patient will receive opioid onlv as long as he/she is awake and activelv demanding doses. This inherent safety factor is eliminated by addition of a continuous infmion (9). The danger is increased by the fact that plasma opioid concentrations, which d o not cause significant respiratory depression in an awake patient, may d o so in a patient who is sleeping ( 18). M'hen choosing a continuous infusion, one must also consider that commonlv used opioid analgesics have elimination half-lives on the order of several hours. Thus, plasma concentrations will continue to increase for some time after initiation of a continuous infusion. A patient who is comfortable and awake after several hours on a continuoi~sinfusion of morphine may be seriously overdosed 24 hor~rslater. A tvpical patientcontrolled analgesia regimen for postoperative pain at the University of Pennsylvania would include a 1 mg demand dose of morphine with a 10-minute lockout period. Continuous infusion rates for morphine are 1 /2 to 1 mg/hour. Some patients will require higher doses. Although some physicians would be concerned about offering such high doses, it should be remembered that these patientcontrolled analgesia settings d o not determine how much drug the patient will get, only how milch they can get. Patients should be instructed in the proper use of patientcontrolled analgesia. They should understand that their goal is near-total pain relief and that there is little to be gained by tolerating distressing pain. It should be explained that there is very little risk of either drug overdose o r development of addiction. as these are two common concerns for pa-

tients. The possibility of side effects should be discussed and patients should understand that they may need to balance analgesia against side effects. Finallv, patients should understand the concept of the lockout period. Otherwise, patients will sometimes become frustrated after quicklv pressing the button many times and receiving no relief.

SPINAL ANALGESIA

Opioids Opioids administered into the epidural o r wtbarachnoid space exert their effect bv stimulating opioid receptors in the dorsal horn of the spinal cord ( 6 5 ) . M'hen activated, these receptors (which are located primarily presvnapticallv on the primary afferent nociceptive fibers) inhibit the transmission of nociceptive impulses to higher order neurons. This effect is segmental (limited to areas of the cord receiving drug) and specific (ie., sparing of motor function). Unlike intravenous administration of morphine, the epidural o r subarachnoid route bypasses the blood-brain barrier and allows high concentrations of the drug to be placed close to the spinal opioid receptors. Spinal injection of morphine thereby affords excellent analgesia while minimizing the concentration of opioid in the plasma and higher central nervous svstem centers. T h e lipid solubility of an opioid is the property which best determines its behavior as a spinal analgesic (.SO, 5. 1). From the epidural space, a drug may follow several routes of uptake (12,.34). It can diffuse across the dura into the cerebrospinal fluid. It can bind to epidural fat o r be taken u p by the epidural venous svstem and carried into the systemic circulation. Diffusion into the posterior spinal radicular arteries allows transport directly into the dorsal horn. Agents with high lipid solubility diffr~seinto and out of these areas quicklv and

are associated with quick onset and brief duration of action (50). Hvdrophilic agents difft~seslowly and, once in the cerebrospinal fluid, are slowly cleared from this aqueous medium. T h e cerebrospinal fluid, therefore, acts as a reservoir of drug which bathes the spinal cord. Accordingly, water-soluble drugs are characterized by long latencies and prolonged durations of action. Hvdrophilic agents become more potent when given epidurallv as compared with intravenouslv because they bypass the blood-brain barrier and, therefore, reach the opioid receptors in greater quantity. With intravenous in-jection, lipophilic opioids are not greatly impeded by the blood-brain barrier and, therefore, less increase in potency is achieved after spinal administration. Because spinal analgesia is segmental, drugs injected into the epidural o r subarachnoid space must reach the level of the spinal cord receiving nociceptive input in order to be effective. Hvdrophilic drugs, such as morphine, remain dissolved in the cerebrospinal fluid and, therefore, are transported by bulk flow to sites distant from the point of injection. Lipophilic drugs d o not remain in the cerebrospinal fluid but rather are rapidlv absorbed by epidural fat and other tissues where thev are cleared by vascular uptake. It is important then to in-ject lipid-soluble drugs, such as fentanvl, close to the level of the spinal cord receiving noxious stimuli. This means that for thoracic and most abdominal procedures, placement of epidural catheters at thoracic levels of the spine is preferred when using lipophilic agent5. Because water-soluble agents are carried away from the site of injection, placement of catheters is less critical when using these drugs. Epidural and subarachnoid opioids can be delivered bv single o r intermittent injection, continuous infusion, o r on demand as epidural patientcontrolled analgesia. Few clinicians are comfortable with the idea \'ohme 24 Sumber 4 October 19% -JOSPT

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CLINICAL

of indwelling subarachnoid catheters because they fear an increased risk of infection, although this risk has never been substantiatecl (6). For this reason, subarachnoid opioids are commonly given by single injection. A subarachnoid bolus of morphine, 0.2-0.5 mg, can provide analgesia for u p to 24 hours o r longer. Epidural opioids are routinely given via indwelling catheters for periods of several days to a week after an operation. Continuous infusions may allow a reduction in side effects when compared with intermittent dosing. Use of epidural patientcontrolled analgesia combines the excellent pain relief afforded by spinal opioids with a mechanism for rapid adjustment of dose by the patient. The normal dose for a single bolus of epidural morphine is 2-5 mg. A standard initial rate for continuous infusions is 0..5-1.0 mg/hour. Typical orders for patientcontrolled analgesia morphine would be 0.5 mg/hour plus a demand dose of 0.4 mg every 30 minutes.

Side Effects T h e side effects associated with use of spinal opioids are similar in nature to those resulting from systemic administration. Common side effects include early and late respiratory depression, pruritus, urinary retention, nausea, and vomiting. Respiratory depression is the most serious side effect of spinal opioid therapy and is characterized as either early o r late, depending on how long after administration it occurs. The mechanism of early respiratory depression is identical to that which occurs after systemic use of opioids. The drug is transported by the vasculature from the site of in-jection to the brain stem with resultant suppression of respiratory drive. T h e onset and magnitude of this effect for a given dose of opioid is similar to what would be expected from an identical dose given by the intramuscular route. Late respiratory depres-

sion can occur after use of hydrophilic opioids and is caused by rostral spread of the drug through the cerebrospinal fluid to the brain stem (8, 25). This tvpicallv occurs about 8-12 hours after a bolus dose and can be life threatening. Patients receiving epidural morphine must, therefore. be observed fbr development of this side effect. Treatment for respiratory depression is the same as for that induced by systemic dosing. Late respiratory depression does not occur with lipophilic opioids. Nausea and vomiting are caused by actiwtion of opioid receptors in the medulla as well as in the gut. Opioid receptors in the brain can be a c t i ~ t e d by the drug delivered through the vasculature o r by rostral flow in the central nervous system. This side effect is dose-related and may be minimized with use of lipid-soluble drugs. Nausea from spinal opioids can be treated with antiemetic drugs. Severe symptoms can be treated with intmvenous naloxone. Use of small incremental doses (0.040.1 mg) may allow relief from side effects without reversal of analgesia. Pruritus is a very common side effect of spinal opioid therapy but is usually mild and does not require treatment. Although not caused by histamine release, antihistaminic drugs can be useful in treating mild pruritus caused by spinal opioids. Severe symptoms can be treated with naloxone as with nausea. Urinary retention is another common side effect of spinal opioids. Naloxone can be an effective treatment, but doses sufficient to promote reversal of analgesia may be required. Bladder catheterization may be necessary for many patients receiving spinal opioids.

Local Anesthetics Local anesthetics can be given by the epidural o r subarachnoid routes o r for peripheral ner~ral blockade to provide postoperative pain relief. Local anesthetics have the unique ability to completely

COMMENTARY

block nociceptive transmission (21). Depending o n the concentration used, local anesthetics can provide analgesia by selectively blocking small nociceptive fibers o r complete anesthesia by also blocking larger sensory fibers. In sufficient concentration, they can also block motor fibers (21). T h e side effects of local anesthetics are mostly related to their ability to block other types of fibers and include hypotension, numbness, and weakness. Because bupivacaine has a long duration of action a n d preferentially blocks sensory fibers rather than motor fibers, it is the most commonly used agent. Peripheral nerves o r nenre plexi can be blocked by single doses of local anesthetic. Prolonged neural blockade can be achieved through the insertion of catheters with repeated dosing o r continuous infusions. Because the side effect5 of spinal local anesthetics are different from those produced by opioids, they are effectively used in combination to achieve enhanced efficacy without additive side effects Typically, very dilute concentrations of local anesthetic (0.05-0.125% bupivacaine) are added to standard doses of opioid to provide improved analgesia with little increase in the incidence of side effects. By blocking afferent input into the spinal cord. local anesthetics may clecreaw the production of central hypersensitization and perhaps help avoid the development of chronic pain yidromes. Similarly, application of local anesthetics may decrease somatic, endocrine, and autonomic reflexes (27, 38). which may lead to improved analgesia, faster rehabilitation, and improved outcome for certain p-oups of patients, particularly those undergoing high-risk procedures (36.37).

CONSIDERATIONS FOR ORTHOPAEDIC SURGERY Orthopaedic procedures can be among the most painful of all operations. The frequent need for early

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pivacaine as high as 0.25% may be postoperative ambulation and physical therapy can exacerbate the suffer- required. Doses this high can cause sensory and motor blockade. As a ing these patients experience. The result, patient mobility may be readvantages of regional anesthesia for duced with an accompanying inpatients undergoing hip and knee crease in the risk of decubitus ulcers. operations has been clearly demonWhen possible, less concentrated sostrated by a number of investigators lutions (0.125%) should be used. and make regional anesthesia popular for these procedures. The benefits When epidural catheters are contraindicated, local anesthetic infused include reduced blood loss, lower incidence of thromboembolic compli- through lumbar plexus or femoral nerve sheath catheters can be used cations, and decreased perioperative effectively (23,47). mortality (37,49,61). Catheters inPain after arthroscopic knee proserted for the purpose of providing cedures can be treated in a fashion intraoperative anesthesia can be left similar to that for open knee operain place to allow continued administions. In addition, intra-articular intration of local anesthetics and opijection of local anesthetics and opioids into the postoperative period. oids is an option. Typically, 20-50 ml Whether outcome is further imof 0.25 to 0.5% bupivacaine are inproved by continuation of this therjected. apy is not yet clear. It seems likely Intra-articular injection of opithat the improved pain relief afforded by postoperative regional anoids can provide long-lasting analgealgesic techniques could facilitate sia at doses too small (0.5-6 mg) to be explained by a systemic analgesic early physical therapy and rehabilitamechanism (28,52). This analgesia is tion. Although many patients undergo- reversed by intra-articular naloxone. ing hip arthroplasty and replacement Opioid receptors have been demonexperience considerable pain preop strated within the inflamed knee eratively, most patients experience joint, and analgesic response from only moderate pain in the postopera- intra-articular morphine only occurs tive period (41). Intravenous patient- in the presence of inflammation controlled analgesia therapy is an (52). This may result from: 1) inadequate and costeffective treatment creased access of the drug to the receptor with inflammation or 2) an for most of these patients, particuincreased number of receptors with larly when combined with a NSAID. inflammation. Minimal side effects The initiation of anticoagulant therhave been reported with this techapy is common in this setting and is nique, probably because little opioid a relative contraindication to the use ever reaches the central nervous sysof indwelling epidural catheters and tem. Analgesia from intra-articular NSAIDs. A single dose of epidural or subarachnoid morphine delivered at opioids may be improved and prothe initiation of anesthesia can prolonged by combination with local vide analgesia for over 24 hours. anesthetics (28). Open knee operations are among Shoulder operations can result in the most painful of orthopaedic prosevere postoperative pain. While syscedures. The need for postoperative temic opioids combined with NSAIDs passive motion and physical therapy will be adequate for most patients, may make control of pain even more brachial plexus blockade with local difficult. Systemic administration of anesthetics can provide superior analopioids and NSAIDs may provide ingesia. Interscalene brachial plexus sufficient analgesia in this setting. block with a single large dose of Frequently, epidural administration .375% bupivacaine administered just of opioids and local anesthetics will before or just after an operation can be necessary. Concentrations of buprovide up to 24 hours of excellent

analgesia (7). Catheters can be inserted into the brachial plexus by the interscalene (45), supraclavicular (62). or infraclavicular (43) routes to allow repeated injection or continuous infusion of local anesthetic.

BALANCED ANALGESIA The term "balanced" analgesia (13) describes the use of multiple analgesic agents to selectively affect several of the physiologic processes involved in nociception: transduction (NSAIDs or steroids), transmission (peripheral and/or neuraxial local anesthetics), and modulation (epidural opioids) . Increasingly, postop erative pain management should he viewed via the stratagem of balanced analgesia. Such combinations of therapy represent the most effective regimens available for control of postop erative pain. They can provide almost complete analgesia after surgery both at rest and with mobilization.

CONCLUSION Satisfactory relief from postoperative pain can be achieved for the vast majority of patients. Most patients can be adequately treated with proper combinations of commonly used agents such as NSAIDs and opioids. Because of widely varying analgesic requirements, proper dosages must be carefully determined for each patient. Patientcontrolled analgesia is a strategy for analgesic administration which simplifies determination of correct analgesic dosages. Epidural or subarachnoid adrninistration of combinations of local anesthetics and opioids is often the most effective method available for treatment of postoperative pain, but generally requires a dedicated anesthesia pain service. There is some evidence to suggest that aggressive postoperative pain management can decrease morbidity in high-risk patients undergoing major operations. Further studies are needed to clarify losrr this issue. Voli~me24 Number 4 Octoher 1996 oJOSPT

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