Pain is an unpleasant subjective experience that is the net
effect of a complex interaction of the ascending and descend- ing nervous systems involving biochemical, physiologic, psy- chological, and neocortical processes. Following initial assessment of pain, reassessment should be done as needed based on medication choice and the clinical situation. Effective treatment involves an evaluation of the cause, dura- tion, and intensity of the pain and selection of an appropriate treatment modality for the pain situation. Whenever possible, the least potent oral analgesic should be selected. Equianalgesic doses should be used when converting from one opioid to another. Pain is dened by the International Association for the Study of Pain as an unpleasant sensory and emotional experience asso- ciated with actual or potential tissue damage, or described in terms of such damage. 1 Pain is an unpleasant subjective expe- rience that is the net effect of a complex interaction of the ascending and descending nervous systems involving biochemical, physio- logic, psychological, and neocortical processes. Pain can affect all areas of a persons life including sleep, thought, emotion, and activities of daily living. Since there are no reliable objective markers for pain, the patients are the only ones to describe the intensity and quality of their pain. Pain is the most common symptom prompting patients to seek medical attention and is reported by more than 80% of individuals who visit their primary care provider. 1 Despite the frequency of pain symptoms, individuals often do not obtain satisfactory relief of pain. This has led to recent initiatives in health care to make pain the fth vital sign, thus making pain assessment equally important as obtaining a patients temper- ature, pulse, blood pressure, and respiratory rate. EPIDEMIOLOGY AND ETIOLOGY Prevalence of Pain Most people experience pain at some time in their lives, and pain is a symptom of a variety of diseases. For some, pain may be mild to moderate, intermittent, easily managed, and have minimal effect on daily activities. For others, pain may be chronic, severe or disabling, all consuming, and be treatment resistant. Thus, identifying the exact prevalence of pain is a dif- cult task. According to the American Pain Foundation, more than 50 million people in the U.S. suffer from chronic pain, 30 PAIN MANAGEMENT Christine K. ONeil LEARNING OBJECTIVES UPON COMPLETION OF THE CHAPTER, THE READER WILL BE ABLE TO: 1. Identify characteristics of the types of pain: nociceptive, inammatory, neuropathic, and functional. 2. Explain the mechanisms involved in pain transmission. 3. Select an appropriate method of pain assessment. 4. Recommend an appropriate choice of analgesic, dose, and monitoring plan for a patient based on type and severity of pain and other patient-specic parameters. 5. Perform calculations involving equianalgesic doses, conversion of one opioid to another, rescue doses, and conversion to a continuous infusion. 6. Educate patients and caregivers about effective pain management, dealing with chronic pain, and the use of nonpharmacologic measures. 487 Chisholm_Ch30.qxd 11/6/06 5:59 PM Page 487 488 SECTION 5 / NEUROLOGIC DISORDERS and an additional 25 million experience acute pain from injury or surgery. 2 About 20% of adults, mostly women and the eld- erly, experience chronic pain such as back pain, headache, and joint pain. Prevalence rates for a variety of different types of pain have been described. The annual incidence of moderate-intensity back pain is 10% to 15% in the adult population with a point prevalence of 15% to 30%. 3 Migraine affects more than 25 mil- lion Americans, and 90% of Americans report some other types of headaches (e.g., tension or sinus) each year. 4 Pain resulting from bromyalgia affects 4 million Americans. 5 Cancer is commonly associated with both acute and chronic pain, and about 70% of those diagnosed with cancer will expe- rience signicant pain. 6 The prevalence of neuropathic pain is unknown because of the lack of epidemiologic studies. Current estimates suggest that approximately 1.5% of the population in the U.S. may be affected by neuropathic pain. 7 However, this gure is probably an underestimate and will likely increase due to the increase in disorders associated with neuropathic pain in the ever-growing older population. Approximately 25% to 50% of all pain clinic visits are related to neuropathic pain. 8 Central neuropathic pain is estimated to occur in 2% to 8% of all stroke patients. 9 The elderly, dened as people 65 years of age and over, bear a signicant burden of pain, and pain continues to be under- recognized and undertreated in this population. The preva- lence of pain in people over the age of 60 years is twice that in those younger than 60 years of age. 10 Studies suggest that 25% to 50% of community-dwelling elderly suffer pain. Pain is quite common among nursing home residents. It is estimated that pain in 45% to 80% of nursing home patients contributes to functional impairment and a decreased quality of life. 11 The nancial impact of pain is considered to be signicant. The National Institute for Occupational Safety and Health esti- mated that the cost of low back pain alone was between $50 billion and $100 billion per year. 12 The American Productivity Audit of the U.S. workforce, conducted from 2001 to 2002, revealed that the cost of lost productivity due to arthritis, back pain, headache, and other musculoskeletal pain was approxi- mately 80 billion per year. 13 The Undertreatment of Pain Despite the growing emphasis on pain management, pain often remains undertreated and continues to be a problem in hospitals, long-term care facilities, and the community. In one series of reports, 50% of seriously ill hospitalized patients reported pain; however, 15% were dissatised with pain con- trol, and some remained in pain after hospitalization. 14,15 Misconceptions about pain management, both from patients and health care providers, are among the most com- mon causes of analgesic failure. Some clinicians may be hesi- tant to treat pain because they do not believe the patients reports of pain or feel the patient is exaggerating symptoms in order to obtain medications. Inadequate clinical knowledge of available pain management strategies, including pharmacologic, nonpharmacologic, and alternative therapy options, also often leads to suboptimal pain management. In one survey, approxi- mately three-fourths of physicians cited low competence in pain assessment as the major barrier to effective pain management. 16 Concerns about opiate misuse, abuse, and diversion also con- tribute to less than optimal pain management and cause providers to exercise caution when prescribing opiates for pain. Misunderstandings about the terms addiction, physical depend- ence, tolerance, and pseudoaddiction are additional obstacles to optimal pain management. Patients may present barriers to pain management by not reporting pain symptoms because of fear of becoming addicted or because of cultural beliefs. Elderly patients may not report pain for a variety of reasons including belief that pain is something they must live with, fear of consequences (e.g., hospitalization or loss of independence), or fear that the pain may be forecasting impending illness, inability to under- stand terminology used by health care providers, or a belief that showing pain is unacceptable behavior. PATHOPHYSIOLOGY Types of Pain Several distinct types of pain have been described: nociceptive, inammatory, neuropathic, and functional. 17 Nociceptive pain is a transient pain in response to a noxious stimulus at nociceptors that are located in cutaneous tissue, bone, muscle, connective tissue, vessels, and viscera. Nociceptors may be clas- sied as thermal, chemical, or mechanical. The nociceptive sys- tem extends from the receptors in the periphery to the spinal cord, brain stem, and to the cerebral cortex where pain sensa- tion is perceived. This system is a key physiologic function that prevents further tissue damage due to the bodys autonomic withdrawal reex. When tissue damage occurs despite the nociceptive defense system, inammatory pain ensues. The body now changes focus from protecting against painful stim- uli to protecting the injured tissue. The inammatory response contributes to pain hypersensitivity that serves to prevent con- tact or movement of the injured part until healing is complete, thus reducing further damage. Neuropathic pain is dened as spontaneous pain and hyper- sensitivity to pain associated with damage to or pathologic changes in the peripheral nervous system as in painful diabetic peripheral neuropathy (DPN), acquired immunodeciency syndrome (AIDS), polyneuropathy, post-herpetic neuralgia (PHN); or pain originating in the central nervous system (CNS), that which occurs with spinal cord injury, multiple sclerosis, and stroke. Functional pain, a relatively newer concept, is pain sensi- tivity due to an abnormal processing or function of the central nervous system in response to normal stimuli. Several conditions Chisholm_Ch30.qxd 11/6/06 5:59 PM Page 488 CHAPTER 30 / PAIN MANAGEMENT 489 considered to have this abnormal sensitivity or hyperresponsive- ness include bromyalgia and irritable bowel syndrome. Mechanisms of Pain Pain Transmission The mechanisms of nociceptive pain are well-dened and pro- vide a foundation for the understanding of other types of pain. 18 Following nociceptor stimulation, tissue injury causes the release of substances (bradykinin, serotonin, potassium, hista- mine, prostaglandins, and substance P) that may further sensi- tize and/or activate nociceptors. Nociceptor activation produces action potentials (transduction) that are transmitted along myelinated A- bers and unmyelinated C bers to the spinal cord. The A- bers are responsible for rst, fast, sharp pain and release excitatory amino acids that activate -amino-3-hydroxy- 5-methylisoxazole-4-propionic acid (AMPA) receptors in the dorsal horn. The C bers produce secondary pain which is described as dull, aching, burning, and diffuse. These nerve bers synapse in the dorsal horn of the spinal cord, where sev- eral neurotransmitters are released including glutamate, sub- stance P, and calcitonin gene-related peptide. Transmission of pain signals continues along the spinal cord to the thalamus, which serves as the pain relay center, and eventually to the corti- cal regions of the brain where pain is perceived. Pain Modulation Modulation of pain (inhibition of nociceptive impulses) can occur by a number of processes. Based on the gate control the- ory, pain modulation may occur at the level of the dorsal horn. 19 Since the brain can process only a limited number of signals at one time, other sensory stimuli at nociceptors may alter pain perception. This theory supports the effectiveness of counterirritants and transcutaneous electrical nerve stimula- tion (TENS) in pain management. Pain modulation may result through several other complex processes. The endogenous opi- ate system consists of endorphins (enkephalins, dynorphins, and -endorphins) that interact with , , and receptors throughout the CNS to inhibit pain impulses and alter percep- tion. The CNS also includes inhibitory descending pathways from the brain that can attenuate pain transmission in the dor- sal horn. Neurotransmitters involved in this descending system include endogenous opioids, serotonin, norepinephrine, - aminobutyric acid (GABA) and neurotensin. The perception of pain involves not only nociceptive stimulation but physiologic and emotional input that contributes to the perception of pain. Consequently, cognitive behavioral treatments such as distrac- tion, relaxation, and guided imagery can reduce pain percep- tion by altering pain processing in the cortex. Peripheral Sensitization, Central Sensitization, and Wind-Up Under normal conditions, a balance generally exists between excitatory and inhibitory neurotransmission. Changes in this balance can occur both peripherally and centrally resulting in exaggerated responses and sensitization such as that observed in inammatory, neuropathic, or functional chronic pain. Pain in these settings may occur spontaneously without any stimu- lus or may be evoked by a stimulus. Evoked pain may arise from a stimulus that normally does not cause pain (allodynia) such as a light touch in neuropathic pain. Hyperalgesia, an exagger- ated and/or prolonged pain response to a stimulus that nor- mally causes pain, can also occur as a result of increased sensi- tivity in the CNS. During normal pain transmission, the AMPA receptors are activated, but the N-methyl-D-aspartate (NMDA) receptor is blocked by magnesium. 16 Repeated nerve depolarization causes release of the magnesium block allowing the inux of calcium and sodium and results in excessive excitability and amplica- tion of signals. Continued input from C bers and subsequent increases in substance P and glutamate causes the activation of the NMDA receptor, a process referred to as wind-up. Wind-up increases the number and responsiveness of neurons in the dorsal horn irrespective of the input from the periphery. Recruitment of neurons not normally involved in pain trans- mission or spread occurs leading to allodynia, hyperalgesia, and spread to uninjured tissues. 20 The wind-up phenomenon sup- ports the observation that untreated acute pain can lead to chronic pain and the belief that pain processes are plastic and not static. CLINICAL PRESENTATION AND DIAGNOSIS Classication of Pain Pain has always been described as a symptom. However, recent advances in the understanding of neural mechanisms have demonstrated that unrelieved pain may lead to changes in the nervous system known as neural plasticity. Since these changes reect a process that inuences a physiologic response, pain, particularly chronic pain, may be considered a disease unto itself. Pain can be divided into two broad categories: acute and chronic or persistent pain. Acute pain is also referred to as adaptive pain since it serves to protect the individual from fur- ther injury or promote healing. 17 However, chronic pain has been called maladaptive, a pathologic function of the nervous system or pain as a disease. Acute Pain Acute pain is pain that occurs as a result of injury or surgery and is usually self-limited, subsiding when the injury heals. Untreated acute pain can produce physiologic symptoms including tachypnea, tachycardia, and increased sympathetic nervous system activity, such as pallor, diaphoresis, and pupil dilation. Furthermore, poorly treated pain can cause psycho- logical stress and compromise the immune system due to the Chisholm_Ch30.qxd 11/6/06 5:59 PM Page 489 490 SECTION 5 / NEUROLOGIC DISORDERS release of endogenous corticosteroids. This situation accompa- nied by decreased range of motion and decreased lung capac- ity can delay recovery from the initial injury. Somatic acute pain arises from injury to skin, bone, joint, muscle, and con- nective tissue, and it is generally localized to the site of injury. Visceral pain involves injury to nerves on internal organs (e.g., intestines or liver) and can present as diffuse, poorly differen- tiated, and often referred pain. Acute pain should be treated aggressively, even before the diagnosis is established, except in conditions of head or abdominal injury where pain may assist in the differential diagnosis. Chronic Pain Chronic pain persists beyond the expected normal time for healing and serves no useful physiologic purpose. Chronic pain may be nociceptive, inammatory, neuropathic, or functional in origin; however, all forms share some common characteris- tics. Chronic pain can be episodic or continuous, or both. Physiologic responses observed in acute pain are often absent in chronic pain; however, other symptoms may predominate. There are four main effects of chronic pain, and these include effects on physical function, psychological changes, social con- sequences, and societal consequences. Effects of chronic pain on physical function include impaired activities of daily living and sleep disturbances. Psychological components of chronic pain may include depression, anxiety, anger, and loss of self- esteem. As a result of physical and psychological changes, social consequences may ensue such as changes in relationships with friends and family, intimacy, and isolation. On a societal level, chronic pain contributes to increased health care costs, disabil- ity, and lost productivity. Management of chronic pain should be multimodal and may involve cognitive interventions, physi- cal manipulations, pharmacologic agents, surgical intervention, and regional or spinal anesthesia. Chronic Malignant Pain Chronic malignant pain is associated with a progressive disease that is usually life-threatening such as cancer, AIDS, progressive neurologic diseases, end-stage organ failure, and dementia. 21 The goal is pain alleviation and prevention, often through a sys- tematic and stepwise approach. Tolerance, dependence, and addiction are often not a concern due to the terminal nature of the illness. Chronic Nonmalignant Pain Pain not associated with a life-threatening disease and lasting longer than 6 months beyond the healing period is referred to as chronic nonmalignant pain. Pain associated with low back pain, osteoarthritis, previous bone fractures, peripheral vascular dis- ease, genitourinary infection, rheumatoid arthritis, and coro- nary heart disease is considered nonmalignant. The numerous causes of this type of chronic pain make treatment complex and involves a multidisciplinary approach. Treatment is initially con- servative but may involve the use of more potent analgesics including opiates in psychologically healthy patients. 22 Neuropathic Pain Neuropathic pain may be considered to be a type of chronic nonmalignant pain involving disease of the central and periph- eral nervous systems. Neuropathic pain may be broadly catego- rized as peripheral or central in nature. Examples of neuropathic pain include PHN, which is pain associated with acute herpetic neuralgia or an acute shingles outbreak. Peripheral or polyneu- ropathic pain is associated with the distal polyneuropathies of diabetes, human immunodeciency virus (HIV), and chemotherapeutic agents. Types of central pain include central stroke pain, trigeminal neuralgia, and a complex of syndromes known as complex regional pain syndrome (CRPS). Complex regional pain syndrome includes both reex sympathetic dys- trophy and causalgia, both of which are neuropathic pain asso- ciated with abnormal functioning of the autonomic nervous system. One of the newest categories of neuropathic pain is neu- ropathic low back pain. The symptoms of neuropathic pain are characterized as tin- gling, burning, shooting, stabbing, electric shocklike quality, or radiating pain. The patient may describe either a constant dull throbbing or burning pain, or an intermittent pain that is stabbing or shooting. Frequent damage to the peripheral nerves may be referred to the body region innervated by those nerves. Traditionally neuropathic pain has been difcult to treat and involves a variety of therapeutic modalities. Rational choice of treatment options may be accomplished through evaluation of the neuropathy and its relationship to peripheral or central nerve damage. Targeting the mechanistic points in the pain pathway is another rationale for treating neuropathic pain. For example, cer- tain opioids, such as methadone, are characterized by NMDA receptor antagonist activity and are effective in treating pain. Anticonvulsant drugs are able to block sodium channels in the peripheral afferent nerve bers. Agents such as tricyclic antide- pressants, bupropion, and venlafaxine block the release of monoamines targeting dorsal horn inhibitory mechanisms. Clinical Presentation of Pain General Patients may be in acute distress (acute pain) or have no signs or symptoms of suffering (chronic pain). Symptoms Pain is described based on the following characteristics: onset, duration, location, quality, severity, and intensity. Other symptoms may include anxiety depression, fatigue, anger, fear, and insomnia. Signs Acute pain may cause hypertension, tachycardia, diaphore- sis, mydriasis, and pallor. Diagnosis The patient is the only person who can describe the inten- sity and quality of their pain. There are no laboratory tests that can diagnose pain. Chisholm_Ch30.qxd 11/6/06 5:59 PM Page 490 CHAPTER 30 / PAIN MANAGEMENT 491 Rating scales provide a simple way to classify the intensity of pain, and should be selected based on the patients ability to communicate (Fig. 301). 27 Numeric scales are widely used and ask patients to rate their pain on a scale of 0 to 10, with 0 indi- cating no pain and 10 being the worst pain possible. Using this type of scale, 1 to 3 is considered mild pain, 4 to 6 is moderate pain, and 8 to 10 is severe pain. The visual analog scale (VAS) is similar to the numerical scale in that it requires patients to place a mark on a 10-cm line where one end is no pain, and the worst possible pain is on the other end. For patients who have dif- culty assigning a number to their pain, a categorical scale may be an option to communicate the intensity of the pain experi- ence. Examples of this include a simple descriptive list of words and the Wong-Baker FACES of Pain Rating Scale. 28 Multidimensional assessment tools obtain information about the pain and impact on quality of life, but are often more time-consuming to complete. Examples of these types of tools include the Initial Pain Assessment Tool, Brief Pain Inventory, McGill Pain Questionnaire, the Neuropathic Pain Scale, and the Oswestry Disability Index. 2933 Pain Assessment in Challenging Populations Children Pain interviews may be conducted with children as young as 3 or 4 years of age; however, communication may be limited by vocabulary. 34 Terms familiar to children such as hurt, owie, or boo boo may be used to describe pain. The VAS is best used with children older than 7 years old. Other scales based on numbers of objects (e.g., poker chips), increasing color intensity, or faces of pain may be helpful for children between 4 and 7 years of age. In children younger than 3 to 4 years, behavioral or physiologic measures, such as pulse or respiratory rate, may be more appropriate. Pain assessment in newborns and infants relies on behavioral observation for such Pain Assessment Effective pain management begins with a thorough and accu- rate assessment of the patient. Even though pain is a common presenting complaint, lack of regular assessment and reassess- ment of pain remains a problem and contributes to the under- treatment of pain. 23 Pain Assessment Guidelines and Regulations for Specic Practice Settings Screening for pain should be a part of a routine assessment, and this has led several organizations such as the Veterans Health Administration and the American Pain Society to declare pain the fth vital sign. Many states have adopted a bill of rights for patients in pain. In 2001, the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) incorporated pain as the fth vital sign in its accreditation standards. 24 According to the JCAHO, patients have a right to appropriate assessment and management of their pain and education regarding their pain. Following initial assessment of pain, reassessment should be done as needed based on medication choice and the clinical situation. Methods of Pain Assessment A patient-oriented approach to pain is essential, and methods do not differ greatly from those used in other medical condi- tions. A comprehensive history (medical, family, and psycho- logical) and physical exam are necessary to evaluate underlying disease processes for the source of pain and other factors con- tributing to the pain. 20 A thorough assessment of the character- istics of the pain should be completed including questions about the pain (onset, duration, location, quality, severity, and intensity), pain relief efforts, and efcacy and side effects of cur- rent and past treatments for pain. A common mnemonic for pain assessment is PQRST (Palliative/Provocative, Quality, Radiation, Severity, and Temporal). 25 Some clinicians have sug- gested the addition of U (you) to this mnemonic. 26 During the pain interview, the impact of the pain on the patients func- tional status, behavior, and psychological states should also be assessed. Evaluation of psychological status is especially impor- tant in patients with chronic pain since depression and affective disorders may be common comorbid conditions. A history of drug and alcohol use should be elicited due to the potential for addiction in patients who may require opiates or other pain medications with a potential for abuse. Other conditions such as renal or hepatic dysfunction, diabetes, and conditions that affect bowel function can inuence therapy choices and goals. A discussion of the patients expectations and goals with respect to pain management (level of pain relief, functional status, and quality of life) should also be part of any pain interview. Pain Assessment Tools Pain, particularly acute pain, may be accompanied by physio- logic signs and symptoms, and there are no reliable objective markers for pain. Many tools have been designed for assessing the severity of pain including rating scales and multidimen- sional pain assessment tools. FIGURE 301. Pain rating scales. (Data from reference 27.) No pain 0 No pain 1 2 3 4 5 Moderate pain 6 7 8 9 10 Worst possible pain Mid pain Moderate pain Severe pain Simple Descriptive Pain Intensity Scale 1 010 Numeric Pain Intensity Scale 1 No pain Pain as bad as it could possibly be Visual Analog Scale (VAS) 2 Very severe pain Worst possible pain 1 If used as a graphic rating scale, a 10 cm baseline is recommended. 2 A 10-cm baseline is recommended for VAS scales. Chisholm_Ch30.qxd 11/6/06 5:59 PM Page 491 492 SECTION 5 / NEUROLOGIC DISORDERS clues as vocalizations (crying and fussing), facial expressions, body movements (ailing of limbs and pulling legs in), with- drawal, and change in eating and sleeping habits. 35 Preschool children experiencing pain may become clingy, lose motor and verbal skills, and start to deny pain because treatment may be linked to discomfort or punishment. School-age children may exhibit aggressiveness, nightmares, anxiety, and withdrawal when in pain, while adolescents may respond to pain with oppositional behavior and depression. Elderly Most of the previously discussed pain scales can be used in older persons that are cognitively intact or with mild demen- tia. The pain thermometer and FACES of pain have been studied in older persons. In persons with moderate to severe dementia or those who are nonverbal, observation of pain behaviors, such as guarding or grimacing, provides an alternative for pain assess- ment. The Pain Assessment in Advanced Dementia (PAINAD) tool may be used to quantify signs of pain and involves observing the older adult for 15 minutes for breathing, negative vocaliza- tions, facial expression, body language, and consolability. 36 Regardless of which pain assessment tool is used, the practitioner should rst determine if the patient understands the concept of the scale to ensure reliability of the instrument. TREATMENT General Approach to Treatment Effective treatment involves an evaluation of the cause, duration, and intensity of the pain and selection of an appropriate treatment modality for the pain. Depending on the type of pain, treatment may involve pharmacologic or nonpharmacologic therapy or both. General principles for the pharmacologic man- agement of pain are listed in the section on patient care and monitoring. Two common approaches to the selection of treat- ment are based on severity of pain and the mechanism responsi- ble for the pain (Fig. 302). Clinical practice guidelines for pain management are available from the American Pain Society, the Agency for Healthcare Research and Quality, the American Geriatrics Society, and the American Society of Anesthesiologists. Selection of Agent Based on Severity of Pain Whenever possible, the least potent oral analgesic should be selected. Guidelines for the selection of therapeutic agents based on pain intensity are derived from the World Health Organization (WHO) analgesic ladder for the management of cancer pain (Table 301). 37 Mild to moderate pain is generally treated with nonopioid analgesics. Combinations of medium-potency opi- oids and acetaminophen or nonsteroidal anti-inammatory drugs (NSAIDs) are often used for moderate pain. Potent opi- oids are recommended for severe pain. Throughout this pro- gression adjuvant medications are added as needed to manage side effects and to augment analgesia. While these guidelines can be useful for initial therapy, the clinical situation (type of pain); cost and pharmacokinetic prole of available drugs; and patient-specic factors (age, concomitant illnesses, previous response, and other medications) must also be considered. Pain medications may also be used in the absence of pain in anticipation of a painful event such as surgery to minimize peripheral and central sensitization. Mechanistic Approach to Therapy Current analgesic therapy is aimed at controlling or blunting pain symptoms. However, diverse mechanisms contributing to the various types of pain continue to be further elucidated. An understanding of these new mechanisms of pain transmission may lead to improvement in pain management, as pharmaco- logic management of pain becomes more mechanism- specic. Use of NSAIDs for inammatory types of pain is an example of a mechanistic approach. Since several mechanisms of pain often coexist, a polypharmacy approach seems rational to target each mechanism. Two current foci in pain management are to identify the mechanisms that are responsible for pain hypersensitivity and to prevent this initial hypersensitivity. Therefore, the goal of pain therapy is to reduce peripheral sensitization and subse- quent central stimulation and amplication associated with wind-up, spread, and central sensitization. 17 Nonpharmacologic Therapy Nonpharmacologic therapies (psychological interventions and physical therapy) may be used in both acute and chronic pain. Psychological interventions can reduce pain as well as Patient Encounter: Part 1 HPI: BA is a 58-year-old male recently diag- nosed with lung cancer. Following surgery he was placed on morphine patient-controlled analgesia (PCA). He has been using 120 mg of morphine/24 hours with ade- quate pain control. PMH: Hypertension x 18 years FH: Noncontributory SH: Lives with wife; has four grown children; smoked 2 packs per day x 40 years (quit with diagnosis of lung cancer) Medications: Hydrochlorothiazide 25 mg every day Pain assessment: Patient rates pain as 8 on a scale of 1 to 10. The physician would like to convert him to a combination preparation of oxycodone and acetaminophen. What dosing regimen would you suggest? Six months later, BAs pain is controlled with the escalating doses of the combination product; however, he has reached the maximum dose of acetaminophen. What would you suggest at this time? Chisholm_Ch30.qxd 11/6/06 5:59 PM Page 492 CHAPTER 30 / PAIN MANAGEMENT 493 the anxiety, depression, fear, and anger associated with pain. Psychological interventions helpful in management of acute pain are imagery (picturing oneself in a safe, peaceful place) and distraction (listening to music or focusing on breathing). Chronic pain patients may benet from relaxation, biofeed- back, cognitive-behavioral therapy, psychotherapy, support groups, and spiritual counseling. Biofeedback teaches patients to control physiologic responses to pain and has been effective in headache and chronic low back pain. Cognitive therapy encourages patients to monitor their perceptions of pain, reducing stress and negativism. Psychotherapy is very useful for patients with chronic pain, and it can also assist in treat- ment of psychiatric comorbidities and help patients to deal with terminal illnesses. 38 The patient should be educated about what to expect regarding pain and its treatment whether pain is acute pain (i.e., preoperative explanations of FIGURE 302. Pain algorithm. NSAID, nonsteroidal antiinammatory drug; AED, antiepileptic drug; SSRI, selec- tive serotonin reuptake inhibitor; TCA, tricyclic antidepressant; SNRI, serotonin-norepinephrine reuptake inhibitor; APAP, acetaminophen. TABLE 301. Selection of Analgesics Based on Intensity of Pain Corresponding WHO Therapeutic Examples of Initial Pain Intensity Numerical Rating Recommendations Therapy Comments Mild 13/10 Nonopioid analgesic; regular Acetaminophen 1,000 mg Consider adding an scheduled dosing every 6 hours Ibuprofen adjunct or using 600 mg every 6 hours an alternate regimen if pain is not reduced in 12 days. Moderate 46/10 Add an opioid to the Acetaminophen 325 mg + Consider step up nonopioid for moderate codeine 60 mg every therapy if pain is pain; regular scheduled 4 hours Acetaminophen not relieved by dosing 325 mg + oxycodone 2 or more 5 mg every 4 hours different drugs Severe 710/10 Switch to a high-potency Morphine 10 mg every opioid; regular scheduled 4 hours Hydromorphone dosing 4 mg every 4 hours WHO, World Health Organization. Data from reference 37. Mild/Moderate Severe Visceral Neuropathic Inflammatory Functional Acute Chronic Pain NSAIDS or APAP Opioids Opioids for Severe Peripheral APAP or NSAIDS TCA or Tramadol Central Opioids Add NSAIDS or APAP Add Adjuvants (e.g., AED, TCA) TCA or AED Lidocaine SSRI or SNRI Long Acting Opioid Ong-acting Opioids (e.g., MS Contin, Oxycontin) SSRI/SNRI Pregabalin Clonidine or Baclofen Chisholm_Ch30.qxd 11/6/06 5:59 PM Page 493 494 SECTION 5 / NEUROLOGIC DISORDERS expected postsurgical pain) or chronic (patient and family education in hospice care). Physical therapy is an essential part of many types of pain sit- uations. Treatment modalities include heat, cold, water, ultra- sound therapy, TENS, massage, and therapeutic exercise. Heat and cold therapy are utilized in a variety of musculoskeletal conditions (muscle spasms, low back pain, bromyalgia, sprains, and strains). Heating modalities include local hot packs, paraf- n wrap, hydrotherapy, and deep-heating methods (ultra- sound). Cold treatments may be delivered via cold packs, ice massage, cold water immersion, or coolant sprays. TENS ther- apy is based on the theory that electrical stimulation of a nerve in a particular area can block pain impulses originating from that area. TENS is also believed to release endogenous endor- phins and enkephalins. Massage therapy is used to relieve mus- cle tension and stiffness and is also felt to increase endogenous endorphins. Therapeutic exercise improves not only strength, endurance, and range of motion, but also provides cardiovascu- lar, psychological, and other health benets. Pharmacologic Therapy Nonopioid Analgesics Acetaminophen Acetaminophen, an analgesic and antipyretic, is often selected as initial therapy for mild to moderate pain and is considered rst-line in several pain situations such as low back pain and osteoarthritis. 39 Mechanistically, acetaminophen is believed to inhibit prostaglandin synthesis in the CNS and block pain impulses in the periphery. Acetaminophen is well-tolerated at usual doses and has few clinically signicant drug interactions except causing increased hypoprothrombinemic response to warfarin in patients receiving acetaminophen doses of more than 2,000 mg per day. The maximum recommended dose for patients with normal renal and hepatic function is 4,000 mg per day. Hepatotoxicity has been reported with excessive use and overdose and the risk of this adverse effect increases in those with hepatitis or chronic alcohol use, as well as those who binge drink or are in a fasting state. Regular chronic use of acetaminophen has been associated with chronic renal failure, but reports are conicting. For these reasons, the maximum dose should be reduced by 50% to 75% in patients with renal dysfunction or hepatic disease and in those who engage in excessive alcohol use. Aspirin and Other Salicylates Aspirin, nonacetylated salicylates, and other NSAIDs have anal- gesic, antipyretic, and anti-inammatory actions. These agents inhibit cyclooxygenase (COX)-1 and COX-2 enzymes, thereby preventing prostaglandin synthesis, which results in reduced nociceptor sensitization and an increased pain threshold. NSAIDs are the preferred agents for mild to moderate pain in situations that are mediated by prostaglandins (e.g., rheumatoid arthritis and osteoarthritis, menstrual cramps, and postsurgical pain) and in the management of pain from bone metastasis, but they are of minimal use in neuropathic pain. Aspirin is effective for mild to moderate pain; however, the risk of gastrointestinal irritation and bleeding limits frequent use of this drug for pain management. Direct effects of aspirin on the gastrointestinal mucosa and irreversible platelet inhi- bition contribute to this risk which can occur even at low doses. Hypersensitivity reactions are also possible and may occur in 25% of patients with coexsiting asthma, nasal polyps, or chronic urticaria. Of additional concern is the potential for cross-sensitivity of other NSAIDs in this group of patients. Nonacetylated salicylates (choline magnesium salicylate and sodium salicylate) have a reduced risk of gastrointestinal effects and platelet inhibition and may be used in aspirin-sensitive patients. Diunisal, a salicylic acid derivative, is associated with fewer gastrointestinal (GI) complaints compared to aspirin, but platelet inhibition does increase the risk of GI bleeding. Nonsteroidal Anti-Inammatory Drugs NSAIDs provide analgesia equal to or better than that of aspirin or acetaminophen combined with codeine, and they are very effective for inammatory pain and pain associated with bone metastasis. 18 These agents may be classied by their chemical structures (fenamates, acetic acids, propionic acids, pyranocar- boxylic acids, pyrrolizine carboxylic acids, and COX-2 inhibitors). While only some members of this class have approval for treat- ment of pain, it is likely that all of them have similar analgesic effects. All members of this class appear to be equally effective, but there is great intrapatient variability in response. After an adequate trial of 2 to 3 weeks with a particular agent, it is rea- sonable to switch to another member of the class. NSAIDs demonstrate a at dose-response curve, with higher doses pro- ducing no greater efcacy than moderate doses, but resulting in an increased incidence of adverse effects (gastrointestinal irrita- tion, hepatic dysfunction, renal insufciency, platelet inhibition, sodium retention, and CNS dysfunction). Patients at increased risk of NSAID-induced gastrointesti- nal adverse effects (e.g., dyspepsia, peptic ulcer formation, and bleeding) include the elderly, those with peptic ulcer disease, coagulopathy, and patients receiving high doses of concurrent corticosteroids. Nephrotoxicity is more common in the elderly, patients with creatinine clearance values less than 50 mL/min, and those with volume depletion or on diuretic therapy. NSAIDs should be used with caution in patients with reduced cardiac output due to sodium retention and in patients receiv- ing antihypertensives, warfarin, and lithium. NSAIDs are classied as nonselective (they inhibit COX-1 and COX-2) or selective (they inhibit only COX-2) based on degree of cyclooxygenase inhibition. COX-2 inhibition is responsible for anti-inammatory effects, while COX-1 inhi- bition contributes to increased GI and renal toxicity associ- ated with nonselective agents. Since the antiplatelet effect of nonselective NSAIDs is reversible, concurrent use may reduce Chisholm_Ch30.qxd 11/6/06 5:59 PM Page 494 CHAPTER 30 / PAIN MANAGEMENT 495 the cardioprotective effect of aspirin due to competitive inhibition of COX-1. For this reason, administration of aspirin prior to the NSAID is recommended. 40 The cardiovascular safety of the COX-2 inhibitors has been questioned due to increased risk of myocardial infarction and stroke seen in several trials. 4143 The Food and Drug Administration (FDA) Committees on Arthritis and Drug Safety and Risk Management convened in February 2005 to evaluate the published studies and manufacturer infor- mation about the cardiovascular adverse events associated with COX-2 inhibitors. 44 As a follow-up to the committees recommendations, the FDA took regulatory action in April 2005, announcing that the increased risk of cardiovascular events was likely a class effect of NSAIDs. A boxed warning highlighting the potential for increased risk of cardiovascular events and GI bleeding is now required for all prescription nonselective NSAIDs and celecoxib. Stronger warnings about these adverse events are also required on nonprescription NSAIDs. As a result of the data and subsequent events, two members of this class, rofecoxib and valdecoxib, have been withdrawn from the market. Future COX-2 inhibitors and nonselective NSAIDs will likely have to undergo cardiovascu- lar safety studies before receiving FDA approval. When a NSAID is needed in a patient with cardiovascular risk, the ben- ets of therapy must outweigh the risk and the lowest effective dose of NSAID is recommended. Opioid Analgesics Opioids are considered the agents of choice for the treatment of severe acute pain and moderate to severe pain associated with cancer. 45 For chronic pain their use was once highly con- troversial; however, use of opioids in chronic pain is now gain- ing acceptance. 46 Opioids may be classied by their activity at the receptor site, usual pain intensity treated, and duration of action (short- versus long-acting). Selection and Dosing The opioids exert their analgesic efcacy by stimulating opioid receptors (, , and ) in the CNS. There is a wide variety of potencies among the opioids, with some used for moderate pain (codeine, hydrocodone, tramadol, and partial agonists) and others reserved for severe pain (morphine and hydromor- phone). Pure agonists (morphine) bind to receptors to pro- duce analgesia that increases with dose without a ceiling effect. Pure agonists are divided into three chemical classes: phenan- threnes or morphinelike, phenylpiperidine or meperidinelike, and diphenylheptane or methadonelike. Partial agonists/antagonists (butorphanol, pentazocine, and nalbuphine) partially stimulate the receptor and antagonize the receptors. This activity results in reduced analgesic efcacy with a ceiling dose, reduced side effects at the receptor, psychotomimetic side effects due to antagonism, and possible withdrawal symptoms in patients who are dependent on pure agonists. Selection of the agent and route depend on individual patient-related factors including severity of pain, individual perceptions, weight, age, opioid tolerance, and concomitant disease (renal or hepatic dysfunction). Since pure agonists are pharmacologically similar, choice of agent may also be guided by pharmacokinetic parameters and other drug characteristics. Hepatic impairment can decrease the metabolism of most opi- oids, particularly methadone, meperidine, pentazocine, and propoxyphene. Furthermore, the clearance of meperdine, propoxyphene, and morphine and their metabolites is reduced in renal dysfunction. Patient Encounter: Part 2 Converting to Different Drugs and Adjusting Doses Two years following his diagnosis of lung cancer, BA has been diagnosed as having bone metastases. Pain has been controlled with the following medications: hydromorphone (Dilaudid) 10 mg IV every hour and levorphanol (Levodromoran) 10 mg orally every 4 hours. He is currently receiving hydrochlorothiazide 25 mg daily, senna two tablets twice daily, and docusate sodium 100 mg twice daily. As the home care pharmacist, you are asked to con- vert this patient to a morphine infusion. Morphine equivalents (based on 10 mg parenteral mor- phine) (Table 302): Hydromorphone 1.5 mg is equivalent to 10 mg of morphine. Levorphanol 4 mg is equivalent to 10 mg of morphine. Based on BAs opioid requirement, recommend an initial infu- sion rate (in milligrams per hour) of parenteral morphine. Which adjuvant therapy could be considered for BA? Recommend a monitoring plan for this patient. How would you assess pain response? TABLE 302. Equianalgesic Doses of Selected Opioids Dose Equianalgesic to 10 mg of Parenteral Morphine (mg) Opioid Parenteral (mg) Oral (mg) Mild-Moderate Pain Codeine 120 200 Hydrocodone N/A 30 Oxycodone N/A 20 Meperidine (Demerol) 100 400 Propoxyphene (Darvon) N/A 65130 Moderate-Severe Pain Morphine 10 30 Hydromorphone (Dilaudid) 1.5 7.5 Oxymorphone 1 N/A Levorphanol 2 4 Fentanyl (Duragesic) 0.10.2 N/A a Methadone (Dolophine) 10 b 35 b a Transdermal: 100 mcg/h = 24 mg/h of IV morphine. b Dosage calculations when converting from morphine to methadone are not linear. The equianalgesic dose of methadone will decrease progres- sively as the morphine equivalents increase (see Table 30-4). Data from references 26, 45, 49, and 51. Chisholm_Ch30.qxd 11/6/06 5:59 PM Page 495 496 SECTION 5 / NEUROLOGIC DISORDERS Table 303 provides a summary of opiate side effects, but sev- eral drugs warrant further discussion. Normeperidine, the active metabolite of meperidine, can produce tremors, myoclonus, delirium, and seizures. Due to the potential for accumulation of normeperidine, meperidine should not be used in the elderly, those with renal impairment, in patients using patient-controlled analgesia devices, or for more than 1 to 2 days of continuous dosing with intermittent dosing. Propoxyphene also has an increased risk of seizures and cardiac conduction abnormalities and should be avoided in the elderly. Despite its popularity, propoxyphene has proven to be no more effective than aceta- minophen, aspirin, or codeine alone. 18 Methadone is unique among the opiates since is it has several mechanisms ( agonist, NMDA receptor antagonist, and inhibition of reuptake of sero- tonin and norepinephrine) that makes it an interesting choice for chronic pain. The long half-life of methadone (30 hours) permits extended dosing intervals; however, the potential for accumulation with repeated dosing often results in challenging dose conversions. Tramadol is a synthetic opioid with a dual mechanism of action ( agonist and inhibition of serotonin and norepinephrine reuptake), and efcacy and safety similar to that of equianalgesic doses of codeine plus acetaminophen. Tramadol has been evaluated in several types of neuropathic pain and may have a place in the treatment of chronic pain. Tramadol is associated with an increased risk of seizures in patients with a seizure disorder, those at risk for seizures, and those taking medications that can lower the seizure threshold. Doses greater than 500 mg have also been associated with seizures. Use of tramadol with other serotonergic drugs (e.g., selective serotonin reuptake inhibitors [SSRIs]) may precipitate serotonin syndrome. While originally thought to be nonhabit forming, dependence may occur with tramadol. About 70% of individuals will experience signicant analge- sia from 10 mg/70 kg of body weight of intravenous morphine or its equivalent. 18 For severe pain in opiate-nave patients, a usual starting dose is 5 to 10 mg of morphine every 4 hours. In the initial stages of severe pain, medication should be given around the clock. Rescue doses should be made available in doses equivalent to 10% to 20% of the total daily opioid requirement and administered every 2 to 6 hours if needed. Alternatively one-sixth of the total daily dose or one-third or the 12-hourly dose may be used. Doses should be titrated based on the degree of pain. One method involves adjustment of the maintenance dose based on the total 24-hour rescue dose requirement. Utilizing dose escalation, doses should be increased by 50% to 100% or 30% to 50% of the current dose, for those in severe and moderate pain, respectively. Once pain relief is achieved, and if treatment is necessary for more than a few days, conversion to a controlled-release or long-acting opioid should be made with an equal amount of agent. Several sustained-release products are available containing morphine, oxycodone, and fentanyl. Some clinicians will reduce the total daily dose of the long-acting dosage form by 25% when initiating a sustained- release product to reduce the likelihood of oversedation. The dose of a pure agonist is limited only by tolerability to side effects. Tolerance may develop to analgesic effects necessitating increasing doses to achieve the same level of pain relief. Physical dependence will also occur with long-term use of opioids. However, addiction or psychological dependence is unlikely in legitimate pain patients unless there are predisposing risk fac- tors. Pain patients who are undertreated may appear to be drug- seeking (pseudoaddiction); however, effective pain management resolves the behaviors. When opioids are used for chronic pain, use of informed consent for chronic opioid therapy and med- ication management agreements or pain contracts may be appropriate to monitor the use (prescribing and dispensing) of controlled substances. Opioids may be administered in a variety of routes including oral (tablet and liquid), sublingual, rectal, trans- dermal, transmucosal, intravenous, subcutaneous, and intraspinal. While the oral and transdermal routes are most com- mon, the method of administration is based on patient needs (severity of pain) and characteristics (swallowing difculty and preference). Oral opioids have an onset of effect of 45 minutes, TABLE 303. Managing Opioid Side Effects Adverse Effects Drug Treatment/Management Excessive sedation Reduce dose by 25% or increase dosing interval Constipation Casanthranol-docusate 1 cap at bedtime or twice daily; senna 12 tabs at bedtime or twice daily; bisacodyl 510 mg daily + docusate 100 mg twice daily Nausea and vomiting Prevention: hydroxyzine 25100 mg (PO/IM) every 46 hours as needed; diphenhydramine 2550 mg (PO/IM) every 6 hours as needed; ondansetron 4 mg IV or 16 mg PO Treatment: prochlorperazine 510 mg (PO/IM) every 34 hours as needed or 25 mg per rectum twice daily; ondansetron 48 mg IV every 8 hours as needed Gastroparesis Metoclopramide 10 mg (PO/IV) every 68 hours Vertigo Meclizine 12.525 mg PO every 6 hours as needed Urticaria/itching Hydroxyzine 25100 mg (PO/IM) every 46 hours as needed; diphenhydramine 2550 mg (PO/IM) every 6 hours as needed Respiratory depression Mild: Reduce dose by 25% Moderate -severe: naloxone 0.42 mg IV every 23 minutes (up to 10 mg) for complete reversal; 0.10.2 mg IV every 23 minutes until desired reversal for partial reversal;may need to repeat in 12 hours depending on narcotic half-life CNS irritability Discontinue opioid; treat with benzodiazepine CNS, central nervous system; IM, intramuscular; IV, intravenous; PO, orally. Data from references 27, 45, and 49. Chisholm_Ch30.qxd 11/6/06 5:59 PM Page 496 CHAPTER 30 / PAIN MANAGEMENT 497 so intravenous or subcutaneous administration may be pre- ferred if more rapid relief is desired. Intramuscular injections are not recommended because of pain at the injection site and wide uctuations in drug absorption and peak plasma concen- trations achieved. More invasive routes of administration such as PCA and intraspinal (epidural and intrathecal) are primarily used postoperatively, but may also be used in refractory chronic pain situations. PCA delivers a self-administered dose via an infusion pump with a preprogrammed dose, minimum dosing interval, and maximum hourly dose. Morphine, fentanyl, and hydromorphone are commonly administered via PCA pumps by the intravenous route, but less frequently by the subcuta- neous or epidural route. Epidural analgesia is frequently used for lower extremity procedures and pain (e.g., knee surgery, labor pain, and some abdominal procedures). Intermittent bolus or continuous infusion of preservative-free opioids (morphine, hydromor- phone, or fentanyl) and local anesthetics (bupivacaine) may be used for epidural analgesia. Opiates given by this route may cause pruritus that is relieved by naloxone. Adverse effects including respiratory depression, hypotension, and urinary retention may occur. When epidural routes are used in narcotic- dependent patients, systemic analgesics must also be used to prevent withdrawal since the opioid is not absorbed and remains in the epidural space. Doses of opioids used in epidural analgesia are 10 times less than intravenous doses, and intrathecal doses are 10 times less than epidural doses (i.e., 10 mg of IV morphine is equivalent to 1 mg epidural morphine and 0.1 mg of intrathecally administered morphine). 45 Combination Analgesics Combinations of opioids and nonopioids often result in enhanced analgesia and lower dose of each. Combination anal- gesics are frequently used in moderate pain. However, in severe pain, the nonopioid component reaches maximum dosage, and thus the usefulness of nonopioids in this situation is lim- ited. Additionally, the combination products are short-acting and often not suitable for chronic therapy. Single agents offer greater dosing exibility than combination products. Opioid Allergy True narcotic allergies are rare and should not be confused with pruritus associated with opiate use. Cross-sensitivity between morphinelike, meperidinelike, and methadonelike agents is unlikely. Therefore, when an individual is allergic to one drug in a chemical class of opioids, it is reasonable to select an agent in another chemical class. For the purpose of drug selection in patients with allergies, mixed antagonists should be treated as morphinelike agents. Tapering of Opioids Tapering of opioids may be necessary once the painful situa- tion has resolved in patients receiving doses >160 mg/d of oral morphine (or the equivalent) or in those with prolonged opioid use. In these situations the dose should be reduced by 15% to 20% each day to avoid withdrawal symptoms. Managing Opioid Side Effects and Drug Interactions Side effects common to all opioids include sedation, hallucina- tions, constipation, nausea and vomiting, urinary retention, myoclonus, and respiratory depression. In terms of medication management, the most frequent are sedation, nausea, and con- stipation. Sedation and nausea are common when initiating therapy and when increasing doses. Nausea can be prevented with a centrally-acting antiemetic (see Table 203). Sedation usually improves with continued therapy but may become intractable at high doses, and stimulants may be needed. Respiratory depression is a serious adverse effect, and usually occurs after acute administration in opioid-nave patients. Tolerance to respiratory depression develops rapidly with repeated doses and is rarely a clinically signicant problem in pain patients, even those with respiratory impairment. Constipation is a signicant adverse effect to which tolerance does develop, and prophylaxis with stimulant laxatives (e.g., senna or bisacodyl) and stool softeners, such as docusate, is recommended. Codeine, hydrocodone, morphine, methadone, and oxy- codone are substrates of the cytochrome P-450 isoenzyme CYP2D6. 47 Inhibition of CYP2D6 results in decreased analge- sia of codeine and hydrocodone due to decreased conversion to the active metabolites (e.g., morphine and hydromorphone, respectively) and increased effects of morphine, methadone, and oxycodone. Methadone is also a substrate of CYP3A4, and its metabolism is increased by phenytoin and decreased by cimetidine. CNS depressants may potentiate the sedative effects of opiates. Opioid Rotation Opioid rotation is the switch from one opioid to another to achieve a better balance between analgesia and treatment-limiting adverse effects. This practice is often used when escalating doses (greater than 1 g of morphine per day) become ineffective. In some settings opioid rotation is utilized routinely to prevent the development of analgesic tolerance. 48 Equianalgesic Dosing of Opioid Analgesics Conversion from one dosage form to another or from one opi- oid to another may be necessary in situations such as ineffective pain control, emergence of side effects, change in patient status, and in formulary restrictions. Equianalgesic doses should be used when converting from one opioid to another. Clinicians should be familiar with the equianalgesic dosing and conver- sion strategies to avoid analgesic failure. Equianalgesic tables serve as a guide for selection of the dosage of the new opioid, but have limitations, as they are often based on single-dose studies and clinical observations. 32 Opioid potency is compared using a reference standard of 10 mg of parenteral morphine. Switching from one dosage form to another of the same opioid (i.e., IV to PO) is relatively simple. The current total daily dose is calculated and the total of the new dosage form is determined using a ratio of the equianalgesic doses. This result is then adjusted based on the usual dosing frequency of the new form. Chisholm_Ch30.qxd 11/6/06 5:59 PM Page 497 498 SECTION 5 / NEUROLOGIC DISORDERS When converting to a sustained-release form of the same opioid, dosage may be reduced by 25% to avoid initial sedation; how- ever, the specic product literature should also be consulted. The rst step in an opioid rotation is to calculate the patients total daily dose of opioid based on the regularly sched- uled dose and the total amount of rescue dose needed in 24 hours. This total is then converted to morphine dosing equiva- lents using equianalgesic doses (see Table 302). The total daily morphine dose is then used to calculate the daily dose of the new opioid using dosing equivalents from an equianalgesic table. Since cross-tolerance may not be complete between opi- oids, some references suggest that the calculated equianalgesic dose be reduced by 25% to 50%. 49 If the opioid switch is due to uncontrolled pain, a dosage reduction may not be needed. The equianalgesic dose may need to be reduced more in the med- ically frail and when converting to methadone. 50 Using the commonly cited equianalgesic dose of morphine to methadone (10 mg morphine:10 mg methadone), methadone doses should be reduced by 75% to 80%. However, this ratio is not applica- ble even in patients tolerant to low doses of morphine. 51 Methadone appears to be much more potent than once believed, and morphine:methadone ratios vary according to the total dose of morphine taken at the time of making the conver- sion to methadone (Table 304). 52,53 Conversion to methadone is a complex process, and several different strategies have been proposed including a switch of the entire dose in one day or a gradual conversion over 3 days. Adjuvant Agents for Chronic Pain The role of NSAIDs and opioids in chronic nonmalignant pain has been discussed; however, a review of adjuvant agents for chronic pain, particularly neuropathic pain, is warranted. Adjuvant analgesics are drugs that have indications other than pain but are useful as monotherapy or in combination with nonopioids and opioids. Common adjuvants include antiepilep- tic drugs (AEDs), antidepressants, antiarrhythmic drugs, local anesthetics, topical agents (e.g., capsaicin), and a variety of miscellaneous drugs (e.g., NMDA antagonists, clonidine, and muscle relaxants). There is little consensus as to the optimal management of neuropathic pain, because much of the evidence for treatment effectiveness consists of anecdotal reports or poorly designed trials. Published guidelines have been suggested for the general management of neuropathic pain. 54 Suggestions for rst-line therapy include gabapentin, lidocaine patch, or tricyclic antide- pressants (TCAs) (Table 305). 5458 Newer antidepressants, such as the SSRIs, have fewer side effects but appear to be less effective than the TCAs for neuropathic pain. However, sero- tonin-norepinephrine reuptake inhibitors (SNRIs) (e.g., dulox- etine and venlafaxine) have been used successfully for painful DPN. A stepwise approach is suggested for managing the patient with neuropathic pain, beginning with the least invasive effective therapeutic choice and proceeding to the rational use of multiple drug regimens. To guide the choice of pharmaco- logic agents, patients may be identied as candidates for AEDs, TCAs, or opioids based on the presence of peripheral or central nerve pain and description of symptoms (see Fig. 302). Choice of agent may also depend on dosing frequency and comorbidi- ties. Data on combination therapy are lacking, and the use of combined treatment is empirical based on additive therapeutic benet. Scheduled medication regimens instead of as needed TABLE 304. Methadone Dose Conversions Total Daily Dose Morphine: Oral Morphine Methadone Factor <100 mg 3:1 3 mg morphine: 1 mg methadone 101300 mg 5:1 301600 mg 10:1 601800 mg 12:1 8011,000 mg 15:1 >1,000 mg 20:1 Data from reference 53 with permission. TABLE 305. Selected Adjuvant Analgesics and Suggested Dosing FDA-Approved Agent Dosing Guidelines Indication Amitriptyline 1025 mg at bedtime with (Elavil) weekly increments to a target dose of 25150 mg of amitriptyline or an equivalent dose of another TCA Duloxetine 60 mg daily DPN (Cymbalta) Gabapentin Initially, 300 mg three times PHN (Neurontin) daily up to a maximum of 3,600 mg daily, in divided doses a Pregabalin DPN: Initially, 50 mg three DPN (Lyrica) times daily; may be and PHN increased to 100 mg three times daily within 1 week based on efcacy and tolerability a PHN: Initially 75 mg twice daily or 50 mg three times daily; may be increased to 100 mg three times daily within 1 week based on efcacy and tolerability a Lidocaine 5% Up to three patches may be PHN (Lidoderm applied directly over the patch) painful site once daily; patches are applied using a regimen of 12 hours on and 12 hours off a Dosing for creatinine clearance of 60 mL/min or greater. DPN, diabetic peripheral neuropathy; PHN, post-herpetic neuralgia; TCA, tricyclic antidepressant. Data from references 5458. Chisholm_Ch30.qxd 11/6/06 5:59 PM Page 498 CHAPTER 30 / PAIN MANAGEMENT 499 dosing should be employed when treating chronic pain, and the effectiveness of therapy should be reassessed regularly. If patients are managed on a multiple drug regimen and changes are indicated, changing only one drug at a time is suggested. Topical agents (e.g., capsaicin) may be added to a regimen to reduce the oral medication load, particularly if adverse effects are a problem or if pain is not relieved. Complementary and Alternative Medicine Complementary and alternative medicine (CAM) is a term used to encompass a variety of therapies (e.g., acupuncture, chiropractic, botanical and nonbotanical dietary supplements, and homeopathy) not typically taught in medical and allied health schools. Painful conditions are among the most common reasons individuals seek relief from CAM. In a recent survey, neck pain, joint pain, arthritis, and headache were among the top ten reasons for use of CAM, and low back pain ranked the num- ber one reason for CAM therapies. A variety of dietary supple- ments have been suggested for painful conditions, such as S- adenosylmethionine (SAM-e), ginger, sh oil, feverfew, -linoleic acid, glucosamine, and chondroitin. Of these, glucosamine and chondroitin are the most popular and have the most evidence of efcacy. Glucosamine in doses of 1,500 mg/d is effective in reducing pain of osteoarthritis by repair of cartilage and is rec- ommended by the American Pain Society. OUTCOME EVALUATION Individualize treatment goals at the beginning of treatment. Utilize information obtained during the pain interview to cre- ate goals that are consistent with the patients expectations. Prevention, reduction, or elimination of pain are important goals for treatment of acute pain. With chronic pain, elimi- nation of pain may not be possible, and goals may focus on improvement or maintenance of functional capacity and quality of life. Thus, for example, pain goals may include pain scale less than 3, be able to play a game with grand- children, or be able to knit again. Assess patients periodi- cally, depending on the method of analgesia and pain condi- tion, for achievement of pain goals. Evaluate the patient for the presence of adverse drug reactions, drug allergies, and drug interactions. ABBREVIATIONS AED: Antiepileptic drug AIDS: acquired immunodeciency syndrome AMPA: -amino-3-hydroxy-5-methylisoxazole-4-propionic acid APAP: acetaminophen CAM: complementary and alternative therapy CNS: central nervous system COX: cyclooxygenase CRPS: complex regional pain syndrome CYP: cytochrome P-450 isoenzyme DPN: diabetic peripheral neuropathy FDA: Food and Drug Administration GABA: -aminobutyric acid GI: gastrointestinal HIV: human immunodeciency virus IV: intravenous IM: intramuscular JCAHO: Joint Commission on Accreditation of Healthcare Organizations NMDA: N-methyl-D-aspartate NSAID: nonsteroidal anti-inammatory drug PAINAD: Pain Assessment in Advanced Dementia (tool) PCA: patient-controlled analgesia PHN: post-herpetic neuralgia PO: oral PQRST: Palliative/precipitating, Quality, Radiation, Severity, and Time SAM-e: S-adenosylmethionine SNRI: serotonin-norepinephrine reuptake inhibitor SSRI: selective serotonin reuptake inhibitor TCA: tricyclic antidepressant TENS: transcutaneous electrical nerve stimulation VAS: visual analog scale WHO: World Health Organization Reference lists and self-assessment questions and answers are available at (insert web address here). KEY REFERENCES AND READINGS American Geriatrics Society Panel on Persistent Pain in Older Persons. The management of persistent pain in older persons. J Am Geriatr Soc 2002;50:120. Patient Care and Monitoring 1. Identify the source of pain. 2. Assess the level of pain using a pain intensity scale. 3. Base the initial choice of analgesic on the severity and type of pain, as well as on the patients medical condi- tion and concurrent medications. 4. Use the least potent oral analgesic that provides ade- quate pain relief and causes the fewest side effects. 5. Titrate the dose to one that achieves an adequate level of pain control. 6. Use a dosing schedule versus as-needed dosing. 7. Assess the patient for analgesic effectiveness and for side effects at each visit or more frequently, depending on the acuity of the patients condition. 8. Avoid excessive sedation. 9. Adjust the route of administration if the patient is unable to take oral medications. 10.Use equianalgesic doses as a guide when switching opioids. Chisholm_Ch30.qxd 11/6/06 5:59 PM Page 499 500 SECTION 5 / NEUROLOGIC DISORDERS American Pain Society. Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain. 5th ed. Glenview, IL: American Pain Society, 2003: 1341. Clinical Practice Guideline, Cancer Pain Management. U.S. Department of Health and Human Services, Agency for Health Care Policy and Research. AHCPR Pub. Rockville, MD: 1994. Available at: http://www.ncbi.nlm.nih.gov/books/ bookres.fcgi/ hstat6/ f37_capcf4.gif. Accessed January 10, 2006. Dworkin RH, Backonja M, Rowbotham MC, et al. Advances in neu- ropathic pain: diagnosis, mechanisms, and treatment recom- mendations. Arch Neurol 2003;60:15241534. Joint Commission on Accreditation of Healthcare Organizations. Pain Assessment and Management an Organizational Approach. Oakbrook Terrace, IL: JCAHO,2000:16. Woolf CJ. Pain: moving from symptom control toward mechanism- specic pharmacologic management. Ann Intern Med 2004;140: 441451. Chisholm_Ch30.qxd 11/6/06 5:59 PM Page 500