onan Pain Management TERRY J. BAUMANN, JENNIFER Ni, STRICKLAND, AND CHRIS M, HERNDON KEY CONCEPTS tis important, whenever possible, to ask patients if they have po P "y pain, to identify the source of pain, and to assess the charac- teristics of the pain. © Patients taking analgesics should be monitored for response and side effects, particulary sedation and constipation assoc ‘ated with the opioids. © Oral anelgesics are preferred over other dosage fois when- fever feasible, but it is important to adjust the route of admin- istration to the needs of the patient © Equonalgesic doses are useful as 2 guide when converting from one agent to another, but further dose tivation usualy is required to achieve treatment goals © Doses must be individualized for each patient and admin. istered for an adequate duration of time. Around-the-clock regimens should be considered for acute and chronic pain. Asmneeded regimens should be used for breakthvough pain or when acute pain displays wide variability and/or has subsided greatly, For chronic pain that has a maladaptive inflammatory and/or ‘neuropathic. component, anticonvulsants, topical analgesics, tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, and opioids should be considered, @ Whenever possible, a mutidiscipinary approach and nonphar- macologic strategies should be used, lacebo therapy should not be used as an attempt to dia Placebo therapy should not be used pt to diag nose psychogenic pain AlUhough the world ful of suffering ts ofl of Se overcoming oft Helen Keller! ‘Humans have always known and sought relief from pain? Today, paln’s impact on society sill great, and indeed pain complaints remain a primary reason patients seee medical advice.” Regrettably, many healthcare providers do not receive adequate training inthis area, and new information isnot widely disseminated Leaming objectives, review questions, and other resources can be found at ‘www.pharmacotherapyonline.com. andior understood, Clealy, pain management is enhanced when 1 multidisciplinary approach is applied. Thus, understanding the pathophysiology of pain therapy and maintaining a working knowl- edge of individual pain regimens are important Key factors in addressing pain contrl DEFINITION “The accepted current definition of pain s:*an unpleasant sensory and emotional experience associated with actual or potential tissue dam- tage or described in terms of such damage. Pain often isso subjec: tives however, that many clinicians define pain as whatever the patient sy itis, The best cate is achieved when the patient comes firs. EPIDEMIOLOGY Data from the National Health and Nutrition Examination Survey Indicate that 1 in-4 Americans have suffered pain that lasts for more than 24 hours in the previous month and in those reporting pa, 4296 state that it lasted more 1 yea.*Seventy-sx and a half milion Americans report they ate in chronic pain; ths is more than the umber of patients with heart disease, cancer, and diabetes com- bined.* The annual cost of pain to US. society can be estimated to be in the billions of dollars*” In 1 year an estimated 25 million Americans will experience acute pain due to injury or surgery, and ‘one-third of Americans will experience severe chronic pain at some point in their ives. These numbers ae expected to rise, a increas ingly more Americans work beyond age 60 years and survive into thc 80” The 106th Congress passed Title VI, Section 1603, of H.R. 3244 which declared a 10-year interval starting January 1, 2001, the “Decade of Pain Control and Research”, Unfortunately, despite ‘uch public attention, considerable focused education, anda num- ber of consensus guidlines, pain often remains underestimated and, ‘undertreated.!**" PATHOPHYSIOLOC “The pathophysiology of pain involves a complex array of neural networks inthe brain that are acted on by afferent stimuli to pro- duce the experience we know as pain, In acute pain, this encounter is short lived; but in some situations the changes may persist, and chronic pain develops. NOCICEPTIVE PAIN [Nociceptive pain typically is classified as either somatic (arising from skin, bone, joint, muscle, or connective tissue) or visceral 1045process decreases the ea more dfficlt 1047 CCharactrists of Acute and Chronic Pain Cuncite helen Cea sa fer az 5 wiltiple © It is pain caused by the disease itself a eg Therefore, a comprehensive history and physical examination re imperative to evaluate underlying diseases and possible other contributing factors’ This includes asking if the patient has pain and identifying the source of pain when possible, however, the baseline characterization of pain can be obtained by assessing haracterstics outlined in Table 69-2 side effects (eg. opioid-induced sedation or constipation) must be sessed and reassessed on a regular basis. The timing and regu ty ofthis assessment will depend on the typeof pain and the medi ations administered. Postoperative pain and acute exacerbation four “A's (analgesia, activity, aberrant drug behavior, and verse effects) as key assessment measures for any patient with hronie pain CCharactristis of Pain esthe pa1048 It is important to note that often objective lacking for pain evaluation, Acne pein may rem ini pathetic tone (eg. hypertension, tachyeardia, tchypnes): however, this pain. The clinician must rly onthe patents description of thei pl . eer ; General %. shanges in feeding habits, increased fussiness. with depression, fatigue, anger, and fear in particular, are noted to lower this threshold, whereas test, mood elevation, sympathy derstandin Symptoms CCan be described as sharp, dul, shock like, tingling, shooting ating, fluctuating in intensity, and varying in location (thes Signs enerally re Laboratory Tests Pain is always subjective There are no specific laboratory tess for pal Pain is best diagnosed based on patient description and history Chronic General no noticeable suferin threshold. Anxiety, depression fatigue, anger, and far in ticular, are noted to lower this threshold; whereas rest, mood Symptoms Can be deseribed as sharp, dull, shock-like, tingling, shoot ng, radiating, fluctuating in intensity, and varying in location lahese often occur without a timely relationship with an obvi Over time, the pain stimulus may cause symptoms that com pletely change (eg. sharp to dull, obvious to vague Sign are seldom present in most cases there are no obvious signs Comorbid conditions often present (eg. insomnia, depre Outcome of treatment often unpredictal Laboratory Tests sin i best diagnosed based on patient description and histo There are no specific laboratory tests for pain; however, history andi diagnostic proof of past trauma (eg may be helpfl in diagnosing etiology. Gener may bec d inchide vitamin D levels, thyr in antibodies, and B, physical manipulation, application of heat or cold, massage, and tic, neuropathy, and masculoskeletal pain). However, published ding long-term benefits limited. As a result, routine 1d hypnosis, have proven effective in the man Moderate evidence and biofeedback Many consider pharmacologic treatment to be the cornerstone of Analgesia should be initiated with the most effect having the fewest side effects. Acetaminophen, acetylsalicylic acid aspirin), and nonsteroidal antiinflammatory drugs (NSAIDs) often, re preferred over opiates in the treatment of mild-to-moderate pain (Lable 69-3). rugs (with the exception of acetamino phen) prevent formation of prostaglandins produced in response oxiou impulses ceived by the CNS." NSAIDs may be particularly useful in the efficacy of these agents have been inconsistent. Therefore, the kinetics, p profil, Because of the aige interpatient variability in response to vlvidual NSAIDS, itis considered rational therapy to switch t nother member ofthis class if there is inadequate response after ficient therapeutic trial of any single agent." The du/Adlt FDA-Approved Nonopiid Analgesics (Includes Only FDA-Approved Agents for Pain) Aoprosinate ls nd Generic Name (rand Name) Wale) Usa Dosage Range ng) Mazit Dose (gay) Salts a 5-160 4 7 : nt ' ¥ 0 cen sh rx aminophenl Fenamats tec . ance acd ten mb a nds Propionic acs pod Froiain arbor acd ws : so rants ‘ fed y arate 20 aplolde axe @fhen the new logical step ta fhe menagesnent of acute ing guidelines are outlined in Tables 69-4 and 69-5. Opiate pein and cancer-related chronic pein. They sleo may be an effective i choice shouldbe based on patient acceptance; analgesic fective however, this continues tobe somevthatcontoversiaL Many times : 1 ial of opioids is warranted, but such tal sould not be done MONSCT Nan sessment ofthe pnt’ factonlty and skfacars repli ead y the apa aos emery 1049 quawaBeuey leg1050 Opioid Analgesics, Central Analgesics, Opioid Antagonist (lass and Generic Name Relative Histamine (Grand None) Chemica Souce Release Prenntrenes (meri ean mortene (ini f fal ering) s g ef tural $F ——_rhenvieiesinepei he aen ete Dene Sy Diphenepaes (methadone ke agoi) here ec ¥ Agont-ntagoit derives : ree v hao atl re ¥ Aaagnis Cetra antes ol sy ¥ prt rt i 10 may further differ among agents because of recep tor subtype variability." This y-receptor subtype variability may plain why some patients respond differently to certain opiokd ifcally w-receptor a The effects oft gesics are relatively selective, and at normal therapeutic alect other sory modalities, hearing undesirable side effects may increase as the dose is escalated Equianalgesic Dose in Approximate Onset Route Adal (mg) (iy Malte W 0 Wu pioids with no unwanted side effects, but as nts may not tolerate even very low doses.” F ploids are administered, pain is not eliminated, but its unpleasa eased." Patients report that although their pain is stil to longer bothers them, hare related pharmacologic attributes and exert a pro ston the CNS and gastrointestinal tract." Mood change rausea, vomiting, decreased. gasteointestinal moti re evident in varying degrees with all agents." Tolerance to sideAgents) 1051 Dosing Guidelines Doses (Use Lowest Efective Dose, Titate Up ‘or Down Based on Patent Response, Opiohd Tolerant Patents May Need Dose Medifition) Notes1052 Dosing Guidelines (continued) Doses (Use Lowest Efective Dose, Tate Up ‘or Down Based on Patient Response, Opioid ‘Agenis) Tolerant Patents May Need Dose Mediation) Notes i 0 gd ec ine ant rod ; omg da inate vith dere pat penopine M03 mge econ ine agent fr md a pate vith nde pate areal (51 ith " nate be elev in evering resp depres Jaxon 2 nei of eds paterts needing ange ate (01-02 a i dose a enpatmer andi he ele de rl 7 7 : " ser second doe te teeth of the most appropriate agent. @ The route of administration acts much like the morphine-like agonis due to his Jepends on individual patient needs, In patients who have amine release may be reduced by choosing agents shown to have access, the oral route is preferred. However, the onset of analge- less effect on histamine release. Morphine has been associated with effects for oral medications is approximately 45 minutes, and the greatest histamine release, whereas oxycodone the peak effect usually occurs 1 to 2 hours after administration," and fentanyl typically cause fewer histamine-rlated reactions (se This delay must be a consideration when immediate relief is Table 69-1 needed in the management of acute pain, Therefore, in some In the inital stag ste pain, analgesi be ‘enarios, sich as acute severe pain (i. pain crisis) or when the given around the clock. This should commence after administering Patient is unable to take oral medications alternative routes of atypical starting dose and titrating up or down, depending on the therapy (eg. intravenous) may be preferte lative potenc dent's degree of pain and demonstrated side effects (e.g, sed defined by the equianalgesie dose, of opioids differs greatly on) As-needed schedules often produce wide swings in analgesic Table 69-1). @ Equianalgesic dose tables ate often based on plasma concentrations thatcreate wide swings in pain and sedation, ngle-dose studies without regard for patient variability and This may initiate a vicious cycle where inereasing amounts of pain ld be used only asa guide.* True opioid alle rare,but medications are needed for relief. @ As the painful state subsides Table 69-- also can be used when treating a patient who i allergic and the need for medication decreases, as-needed schedules ma to opiates. Most reactions to opioids, such as itching or rash, ate be appropriate. As-needed schedules also may be useful in patients Jue to the associated histamine release from cutaneous mast cells, who present with pain that is intermittent or sporadic in nature not a true allergic or immunoglobulin-E (IgE) or T-cell response.” (Fig, 69-2). When opioids are used inthe management of persist Although caution is always advised, a decrease in potential chronic pain, around-the-clock administration schedules should ross-senst hought to exist when moving from one opi- be utilized. As-needed or PRN opioids should be used in conjun oid structural class to another.” The classes are phenanthrenes tion with around-the-clock regimens and when patients experience norphine-Like agonists), phenylpiperidines (meperidine-like ago- breakthrough pain, Breakthrough pain isa brie, transitory, exacer nists), and diphenylheptanes (methadone like s). When bation of moderate to severe pain typically occurring inpatients with onsidering cross-sensitivity, the mixed agonist-antagonist c underlying persistent pain that may otherwise be controlled Continuous intravenous and subcutaneous methods of opioid infusion are effective for some postoperative pain, but the pro Major Adverse Effects ofthe Opioid Analgesics ity of unwanted side effects is high, and this technique should == Tee 7 reserved for opioid tolerant patients An alternative method [ patient-controlled analgesia (PCA), With this technique, patents can : sprite self administer ap ‘of an intravenous opioid via a pump cl inn incre : . onically interfaced witha timing device. Compared with traditional 0. a s-needed opioid dosing, PCA yields better pain control, improved ed gestetesta patent satisfaction, and relatively fee diferences in side effects ase phi spas dministration of rectly into the CNS (eg. epidural c en ind intrathecal/subarachnoid routes) has shown considerable Oe . pain (Table 69 1nd is common in both small stitutions throughout the United States, Because sof ne Iona ev n, and hypotension.” these methods of analgesia require care m 1 monitoring and are { by experienced practitionersRespiratory depression is of concern and can oceur within minutes with ith intrathecal fentanyl or manifest as late as 19 hours after a single dose of intrathecal morphine.” Guidelines mandate respiratory dire monitoring for at last 24 hours after a sing intrathecal or epidural morphine.” Naloxone is used to antagonize this effect. Analgesia and side eflects are evident at lower doses when opiokds barrier are administered intrathecally instead of epidually.Inteathec pai durally, doses of 1 to 6 mg are the norm.” These intrathecal and drug ef dural opioids often are administered a8 a comtinuous-infusion at d and/or on a patient-controlled basis. When given simultaneously stable di 1053 thecal or epidural local anesthetics such as bupivacaine been proven safe and effective” All agents administered into the CNS should be preservative free ne misunderstanding of opioid tolerance, physical depen: fect overtime as a result of exposure to the drug,” It develops nt rates and with great patient variability. However, with isease opioid use often stabilizes and tolerance does nat lead1054 srapiosig 2480jonaN Intraspnal Opioids Onset of Duration Continual Single Pain Raliel of Pain Infusion Agent Dose mg) (min) Ree (h)_Dose mg/h) Epidural route Subarachooid route to addition.” “Physical dependence is defined by the occurrence of 1 to addiction; however, with chronic opioid use ding toPortenoy.” “Addict over drug use, compulsive drug use, and continued use of a drug despite harm,” When opioids are being used, these behaviors must be evaluated continually, However, caution is advised when using the term addiction because of its many negative connotations, which can lead toa compromised clinician-patient relationship and. aware that an individuals behavio diction, when in realty the behaviors noted are a relletion of unselieved pain, depending on the patient swith no history of ction, the isk o dito isk for Morphine can be Side effects can be numerous, particularly when morphine is ased. Morphine first initiated or when doses are significantly to patients not experiencing pain.” As doses of morphine are lioxide, causing progressive respiratory depression.” This effect is less pronounced in patients being treated for severe or chronic pai. 's potentially harmfil and possibly etal ie more susceptible to morphine-in decreases in blood pressure)” Because morphine prompts decrease in myocardial oxygen demand in ischemic cardiac patients." itis often considered the drug of choice when using opi is to treat pain associated with myocardial infarction rphine di ence is unclear, Urinary retention is another potential side eflect of dicated in head injur rug induced respiratory depression can intracranial pressure. Thus, caution is advised in head trauma sure” and cloud the neurologic examination results Morphine is metabolized to two major metabolites, morphine tributes to analgesia, whereas M3G may contribute to side ffects™ The metabolites are renally cleared and can accumulate patients with renal impairment, contributing to greater side fects” Morphine also affects the hypothalamus inhibiting the lease of gonadotropin-relasing hormone, thus decreasing plasma testosterone and cortisol” Although the clinical meaning has no Jearly been elucidated, morphine and other opioids also appea immunosuppressive morphone is more potent, has better oral absorption characteristics, and is more soluble than morphine, but its overall harmacologic profile parallels that of morphine, Some clinicians lieve hydromorphone is associated with fewer side effects, espe side effects between morphine and hydromorphone. Oxymorphone an be administered otally, rectally, and by injection. Although xtended-release and immediate-release oral products have become able, making oxymorphone useful in chronic and acute pan, tofers no pharmacologic advantage Levorp an extended half-life, bu its overall therapeutic effec wderate pain It often is combined with other analgesic product (¢ acetaminophen). Unfortunately, thas the same propensity side effects as monphine, Hyd is anothe ton products with other analgesic agents (eg. acetaminophen, ibuprofen), Its pharmacologic properties are similar to those of wrphine characteristic, the availability of an immediate-release ind contrlled-release oral dosage form also makes it very useful inh that of morphine 9, i 6 notes potent and has a duration. Meperidine offers n icity (CNS h ite normeperidine),* and should be over morphine, has grater periritablity caused b n particular, avoid long-term usage, nd use in patients Fentanyl is a synthetic opioid structurally related meper dine that is used often in anesthesiology as an adjunct to general anesthesia." This agent is more potent and faster acting than mep ridine (Table 69-4). It can be administered parenterally, ransmu osally, and tran lermally Methadone has gained consider able popularity because of its oral efficacy, extended duration of action, and low cost, Although methadone is effective in Pain, thas gained particular prominence in treating cancer and has increasingly been used in the management of chron noncancer pain. This despite the fact that, with repeated doses, the analgesic duration of action is prolonged it has an unpre diciable half-life, it can cause excessive sedation, and itis dificult to titrate. Properties unique to methad pared with other oid, include the b-isomer's ability to antagonize NMDA recep serotonin and norepinephrine reuptak: se properties may used concurrently with other agents that pro is warranted because they believe that neuropathic pain i often Propoxyphene wsuall mbination phen for treatment of mild to mi ote.” Propoxyphene has been associated with medication inju US. Food and Drug Administration (FDA) has recently required more specific product labeling outlining this agent's possible risks Analgesic agents that this in mind. This analgesic class produces analgesia and has a & lover abuse potential than does morphine, but peychotom metic responses (e rcinations and dysphor with withdrawal in opioid-dependent populations" have diminished apentadol also binds the g-opiate jorepinephrine reuptake, Tramadol is indicated for the relief of oderate to moderately severe hile tapentadol is indicated Both tramadol and tapentadol have side-effect profiles similar hat ofthe previously mentioned opioid analgesics (eg, diz ess, nausea, somnolence, and constipation)" Tapentadl is a chedule Il controlled substance, while tramadol isnot scheduled, apentadol has not been systematically evaluated in patients with seirure, and it should be used with caution in seizure pati Seizure risk may be elevated in patient taking tramadol." Tramadol, xy have a place in treating patients with chronic pain, especial europathic pain,” while tapentadal may be most useful in the snagement of acute pain, avant ics are phar je agents with individual haractristcs that make them useful in the management of pain but that typically are not classified as analgesics. Exam Anticonvulsants (e.g, gabapentin, which may decrease neuronal excitability), tricyclic antidepressants serotonin and norepineph: ne reuptake inhibitor antidepressants (which block the reuptake f serotonin and norepinephrine, thus enhancing pain inhibi on), and topically applied local anesthetics (which decrease erve stimulation) all have been effective in managing chronic In cancer patients, bone pain can be treated with radiopharma ceuticals. Both strontium-89 and samarium 153Sm lexidronam have been shown to provide pain relief Although antihistamine imphetamines, and steroids have been used as adjuvant pain dications.” they have demonstrated only limited success as pain lieve. he combination of opioid and nonopio‘d analgesics often results analgesia superio produced by ether agent alone." This wer doses and a more favorable side- his approech is eacoureged lie ofboth acute and chronic pain (Table 69-9)" These ents can be positioned by injection (gin joints, in the epidural intrathecal space, along nerve roots, of in a nerve plexus) or pically. Lidocaine in the form of a patch has proven effective ating focal neuropathic pain.” Regional application of local 1055 quawaBeuey leg1056 srapiosig 2480jonaN Pharmacologic Management of Chronic Noncancer Pain Type of Pain Nonopiids Opioids abicy taco be hep eve pain by blocking nerve impulses." Hi including dizziness, tinnitus, drowsiness, disorientation, muscle twitching, seizures, and respiratory arest* Cardiovascular effect include myocardial depression, hypotension, decreased cardia output, heart block, bradycardia, arrhythmias, and cardiac arrest Disadvantages of such methods include the need for skilful techni al application, need for frequent administration, and highly spe The World Health Organ Jon pain intensity ratings from mild, to moderate, to severe An acute pain algorithm outlining how to use these principles is in Figure 6-2, The importance of reassessment and titration ng this process cannot be overemphasized Managing the pain of cancer encompasses both acute and chron management techniques. @ Thus, pharmacologic treatment and tidiciplinary approach to pain reli” The goal is ide Patients with enough pain amelioration to tolerate diagnostic and therapeutic manipulation and permit the patient to function at a level that willallow freedom of movement and choice.” A Local Anesthetics! Agent (rand Name) Onset (min) Duration (h) fsters Amides acai Comments the fa Table given is 9-2 also applies to cancer patients, Special 1 painful sta Individ and outside the ho the ffect this has on the patient cannot be overstated. Pharmacol nalgesi use in on fents is outlined in Figure 69-3. The numerous etiologies that produ ke treate discipli i ommplex, and overall management should be mult ould never be Inall cases of chronic noncancer pain, an integrated system tie approach (such as that often provided by pain clinics), with @ strong emphasis in perception, la and decrease dep drug therapy. Patient ind clinicians must realize that maximally elective treatment ake months or even years. During this time it may become ne sary to use opioids for chronic noncancer pain patients. This has sa source of debate; however, recommendations exist when this Mam py (€4» NSAIDs), thenNSAIDs) dunes: Tete lite he READS” (Seaton these cases that parent or caregiver input becomes paramount pain ( agitation). @ In addition, those living with chronic, debilitating, are that is palliative in nature.” Although care must be taken in nagement as outlined in this chapter are the guiding tenets in he suffering component of pain cannot be overemphasized. Si lief from acute and cancer pain and well-planned treatment re 1057 quawaBeuey leg