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Pain Report #11- Pain Management for the Elderly

Bruce Allen Ferrell, MD
Department of Medicine, Division of Geriatrics
David Geffen School of Medicine at UCLA
Los Angeles, California

Sponsored by Dannemiller

Supported by an educational grant from Purdue Pharma, L.P.


The Older Patient in Pain

Pain is a common complaint among elderly people. For ambulatory care visits, pain related problems are more common than any other complaint. The intensity of pain often correlates with the severity of injury and indicates urgency for treatment. Over time, unrelieved pain, pain that persists, or pain out of proportion to tissue damage, often results in substantial disability and psychological distress.

The prevalence of pain is high in the elderly population. Epidemiology studies of pain in general populations have suffered from the lack of standard definitions for what might be considered “significant” pain. Nonetheless, studies have suggested that the prevalence of pain in community-dwelling older persons may be as high as 25% to 56%. Sources of pain also vary from study to study. Prevalence of back pain has been reported from 21% to 49.5%; joint pain 20.5% to 71%; and headache 1.2% to 50% in persons over the age of 65 years. In general, the most common causes of pain in elderly persons are probably related to musculoskeletal disorders, such as back pain and arthritis. Neuralgia is also common stemming from diseases, such as diabetes and herpes zoster; and from trauma, such as surgery, amputation, and other nerve injuries. Nighttime leg pain (e.g. cramps, restless legs) is also common, as is caludication. Cancer, although not as common as arthritis, is a cause of severe pain. The distress of cancer pain has brought attention to the obligation clinicians have to provide effective pain management, especially near the end of life. Pain is also common in nursing homes. It has been suggested that 45% to 80% of nursing home residents may have substantial pain. Many of these patients have multiple pain complaints and multiple potential sources of pain.

Pain is associated with a number of negative outcomes in elderly people. Depression, decreased socialization, sleep disturbance, falls, adverse drug events, slow rehabilitation, and increased health care utilization/costs have all been associated with either the presence of pain or its treatment in older people. Older patients rely heavily on family and other caregivers near the end of life. For these patients and their caregivers pain can be especially distressing. Caregiver strain and caregiver attitudes can have substantial impact on pain.

The approach to pain management is different in elderly versus younger persons. Older persons may under-report pain. They often present with concurrent illnesses and multiple problems, which makes pain evaluation and treatment more difficult. Elderly persons have a higher incidence of side effects to medications and higher potential for complications and adverse events related to many treatment procedures. Despite these challenges, pain can be effectively managed in most elderly patients. Moreover, clinicians have an ethical and moral obligation to prevent needless suffering and provide effective pain relief, especially for those near the end of life.

How Aging Affects Perception

The effect of aging on pain perception has been a topic of interest for many years. Elderly persons often present with altered presentation of common diseases. For example, older people have been observed to present with apparently painless myocardial infarction and painless intra-abdominal catastrophes. The extent to which these observations are attributable to age-related changes in pain perception remains uncertain. Anatomical studies, as summarized in Table 1, have observed some age-related changes in the nervous system that might alter pain perception. Some of these findings include decreased numbers of various pain receptors in the skin and other organs, altered nerve conduction, and some central nervous system changes that may affect sensory processing. Unfortunately, most of these studies were based on cross-sectional studies of animal and postmortem specimens for which little or no data was actually available or correlated with the pre-mortem pain experiences.

(Figure 1)

Likewise, a large number of physiologic studies of pain perception also exist. These studies typically use a heat probe, electrical stimulation, or other method to induce pain in volunteers in an effort to identify a pain threshold or pain tolerance level. These studies have shown mixed results; some showed increase, some showed decrease, and some showed no change in pain perception with aging in normal volunteers. Moreover, it has been difficult to conduct a formal meta-analysis using all of these studies because of flaws concerning sampling errors and methodological differences. In the final analysis, most investigators have concluded that actual age-associated changes in pain perception are subtle and probably not clinically significant.

On the other hand, elderly people often present with concurrent illness and sensory impairments that may mask pain complaints. Cognitive impairment, sensory neuropathies, visual and hearing impairments all may make communication of pain complaints more difficult and thus appear to be a perceptual problem. Elderly patients may be more stoic, expect pain with aging, fear diagnostic tests or other interventions, and may fear the meaning of pain. These issues make pain assessment and measurement much more difficult.

Classification of Pain

Pain is quite variable in description, character, and intensity among individuals. For the purpose of understanding, predicting, and treating pain, a variety of classification schemes have been used. For diagnostic purposes, it may be helpful to categorize pain as acute or persistent. The old term "chronic pain" is now considered obsolete, and the newer term "persistent" is used to reduce the common biases and negative stereotypes associated with the label "chronic pain patients" in the past. For treatment purposes, it may be more helpful to categorize pain as nociceptive versus neuropathic.

Acute Versus Persistent Pain
Acute pain is defined by its distinct onset, obvious cause, and short duration. Trauma, burns, infarction, and inflammation are examples of pathological processes that result in acute pain. Acute pain is often associated with autonomic nervous system signs, including tachycardia, diaphoresis, or elevation in blood pressure. The presence of acute pain usually indicates an acute injury or acute disease; and the intensity of acute pain often indicates the severity of injury or disease. Thus, acute pain should trigger an urgent search for an underlying cause that might be life-threatening or require immediate intervention. The effective management of acute pain is important to facilitate diagnostic tests. Pre-operative pain management of acute pain makes anesthesia easier and post-operative pain control better. In some cases, management of acute pain can help prevent development of chronic pain syndromes.

Persistent pain is usually defined by its persistence beyond an expected time frame for healing– usually longer than three months. Intensity of persistent pain is often out of proportion to the observed pathology and often associated with prolonged functional impairment, both physical and psychological. Autonomic signs are often absent (exhausted). Underlying causes of persistent pain are often associated with chronic disease and are less remedial.

Persistent pain is often more difficult to manage because the underlying cause is less curable, and many treatment strategies are either short-lived, difficult to maintain, or associated with long-term side effects. Persistent pain usually requires a multidimensional approach to treatment, including use of both analgesic drug and non-drug strategies with attention to sensory, emotional, and behavioral components of the pain experience.

Nociceptive Versus Neuropathic Pain
For treatment purposes it may be helpful to identify the underlying mechanism of pain perception. Treatment aimed at specific pathophysiologic pain mechanisms may be more effective. Pain problems that result largely from stimulation of pain receptors are called nociceptive pain. Nociceptive pain may arise from tissue injury, inflammation, or mechanical deformation. Examples include trauma, burns, infection, arthritis, ischemia, and tissue distortion. Nociceptive-related pain usually responds well to common analgesic medications.

Neuropathic pain results from pathophysiologic processes that arise in the peripheral or central nervous systems. Examples include diabetic neuralgia, postherpetic neuralgia, and post-traumatic neuralgia (post-amputation or “phantom limb” pain). In contrast to nociceptive pain, neuropathic pain syndromes are often persistent and difficult to treat. However, they may respond to non-conventional analgesic medications such as tricyclic antidepressants and anticonvulsant drugs. For these syndromes, it may be important to recognize them early and to begin treatment with adjuvant analgesic strategies before long-term complications of persistent pain develop, including physical and psychological disabilities.

There are other physiological mechanisms of pain including mixed nocicepitve and neuropathic syndromes and pain syndromes of unknown mechanisms. Treatments for these types of pain are more problematic and often unpredictable. Examples include recurrent headaches and some vasculitic syndromes. Finally, psychologically-based pain syndromes are those with psychological factors that play a major role in the pain experience. Examples include somatoform disorders and conversion reactions. These patients may benefit from specific psychiatric intervention, but traditional pain strategies are probably not indicated.

Clinical Evaluation of Pain

Pain assessment is the most important part of pain management. Any pain complaint that has an impact on physical function or quality of life should be recognized as a significant problem. Unfortunately, there are no objective biological markers of pain. The most accurate and reliable evidence for the existence and intensity of pain is the patient’s self-report of the pain.

Pain History and Physical Examination
Assessment of pain should begin with a thorough history and physical examination to help establish a diagnosis of underlying disease and form a baseline description of pain experiences. The history should include questions to illicit:
  • When the pain started
  • What events or illnesses coincided with the onset
  • Where does it hurt (location)
  • How does it feel (character)
  • What are the aggravating and relieving influences
  • What treatments have been tried
Past medical and surgical history is important to identify coexisting disease and previous experience with pain and analgesic use. The review of systems should probably focus on the musculoskeletal and nervous systems because of the frequency of which these pain problems often occur in older persons. Any history of trauma should be thoroughly investigated because falls, occult fractures, and other injuries are common in this age group. In this setting, care must be taken to avoid attributing acute pain to pre-existing conditions. Making this problem worse is the fact that persistent pain does fluctuate with time. Injuries from minor trauma and acute disease such as gout or calcium pyrophosphate crystal arthropathy can be easily overlooked. Finally, many older persons do not use the word "pain," but may refer to their problems as "hurting," "aching," or use other descriptions. It is important to probe for and identify pain in the patient's own words so that references for subsequent follow-up evaluations are clearly established.

A physical examination should confirm any suspicions suggested by the history. Because of the frequency with which problems are often identified, the physical exam should probably concentrate on the musculoskeletal and nervous systems. Tender points of inflammation, muscle spasm, and trigger points should be palpated. Observation of abnormal posture, gait impairment, and limitations in range of motion may trigger a need for physical therapy and rehabilitation. Evidence of kyphosis, scoliosis, and abnormal joint alignments should be identified. A systematic neurological exam is also important to identify potential sources of neuropathic pain. Focal muscle weakness, atrophy, abnormal reflexes, or sensory impairments may indicate peripheral or central nervous system injury. Mottled skin in a denervated extremity, presence of a Charcot joint, orthostatic hypotension, impaired gastric emptying, or incontinence may indicate autonomic nervous system dysfunction that can imply sympathetically-maintained pain or a complex regional pain syndrome.

It is important to assess functional status to identify self-care deficits and formulate treatment plans that maximize independence and quality of life. Functional status can also represent an important outcome measure of overall pain management. Functional status can be evaluated from information taken from the history and physical examination, as well as the use of one or several functional status scales validated in elderly people (see other sections in this article).

A brief psychological and social evaluation is also important. Depression, anxiety, social isolation, and disengagement are all common in patients with persistent pain. There is clearly a significant correlation associated between persistent pain and depression, even when controlling for overall health and functional status. Therefore, assessment should at least include screening for depression. Psychological evaluation should also include consideration of anxiety and coping skills. Anxiety is common among patients with acute and persistent pain, and it requires extra time and frequent reassurance from healthcare providers. Persistent pain often requires effective coping skills for anxiety and other emotional feelings that can be learned.

For those with significant psychiatric symptoms, referral for formal psychiatric evaluation and management may be required. In these patients, cognitive-behavioral therapy, specific counseling, supportive group therapy, biofeedback, or some psychoactive medications may be necessary for developing and maintaining effective coping strategies as well as management of major psychiatric complications. Social networks should also be explored for availability and involvement of family and other caregivers. It has been shown that family and informal caregivers are often involved and can have a substantial impact on overall pain management. Evaluation of caregivers is particularly necessary when complicated or high-tech pain management strategies are contemplated, such as continuous analgesic infusions. Some pain management strategies can place substantial demands on caregivers resulting in considerable caregiver stress. Need for frequent transportation, administration of pain treatments, and technical training may result in substantial stress for non-professional caregivers, and can result in work absence as well as emotional and physical illness.

Pain Assessment Scales
A variety of pain scales are available to help categorize and quantify pain complaints. Results of these scales are helpful in initial documentation and then periodically to maximize treatment outcomes. Results can be recorded in flow charts or graphs, thus making it easy to identify stability or changes in pain over time. Since there are no "gold standards," the validity of pain scales relies largely on face value, correlation with other known scales (concurrent validity), correlation with pain related constructs (convergence), and experience in many populations over several years.

Pain scales can be grouped into multidimensional and unidimensional scales. In general, multidimensional scales with multiple items often provide more stable measurement and evaluation of pain in several domains. Table 2 summarizes some of the multidimensional scales available. For example, the Brief Pain Inventory has been shown to capture pain in terms of intensity, location, and interference with activities. At the same time, multidimensional scales such as the McGill Pain Questionnaire are often long, time consuming, and can be difficult to score at the bedside, making them difficult to use in a busy clinical setting.

Over the last ten years, data has accumulated on some of these scales in older persons. One example of a behavioral scale is the Hurley Discomfort Scale. This instrument was developed for the assessment of discomfort in patients with profound dementia. The scale consists of nine items scored by a trained examiner after observing the behavior of a non-communicative patient. Behavioral observations, such as breathing, vocalization, facial expression, body language, and restlessness, are scored on Likert scales. Testing of the scale has demonstrated reasonable reliability and stability over time. The scale requires some skill and experience to administer, which may be problematic for some clinical settings.

(Figure 2)

Unidimensional scales consist of a single item that usually relates to pain intensity alone. These scales are usually easy to administer and require little time or training to produce reasonably valid and reliable results. The scales have found widespread use in many clinical settings to monitor treatment effects and for quality assurance indicators. Table 3 describes some unidimensional scales that are commonly used, but a large number of variants are available that have similar characteristics and produce similar results. It is important to remember that unidimensional pain scales often require framing the pain question appropriately for maximum reliability. Subjects should be asked about pain in the present tense (here and now).

For example, the interviewer should frame the question, "How much pain are you having right now?" Alternatively the interviewer can ask, "How much pain have you had over the last week?" or "On average, how much pain have you had in the last month?" The latter questions require accurate memory and integration of pain experiences over time that may be more difficult for patients. Recent studies in those with cognitive impairment have shown that pain reports requiring recall are influenced by pain at the moment. Thus, it may be more useful to use unidimensional scales to assess pain frequently at the moment while evaluating pain reports over time, much the way vital signs are used. This is especially true for those with some cognitive impairment.

(Figure 3)

Pain Assessment in Those with Cognitive Impairment
Cognitive impairment, delirium, dementia, Alzheimer’s disease, or stroke can present substantial challenges to pain assessment. Fortunately, it has been shown that pain reports from those with mild-to-moderate cognitive impairment are no less valid than other patients with normal cognitive function. Weiner and associates have shown that these reports are usually reliable (stable over time) as well. Our experience has shown that commonly available instruments, such as those in Table 3, are feasible for use in most patients with cognitive impairment. Thus, most elderly patients with mild-to-moderate cognitive impairment appear to have the capacity to report pain accurately and reliably using commonly available methods.

Patients with severe cognitive impairment may represent substantial challenges, for which no generalized methods for pain assessment have been identified. Although it has been assumed that those in deep coma do not experience pain, it is not clear that such brain damage necessarily results in complete anesthesia. Patients with “locked-in syndrome” (having intact perception and cognitive function, but no purposeful motor function and no means of communication) may suffer severely. Unfortunately no reliable methods exist to assess pain in these individuals. Healthcare providers must be aware of these situations and provide analgesia empirically, especially during procedures or for conditions known to be uncomfortable or painful. More often, the majority of patients with severe cognitive impairment can and do make their needs known in simple yes or no answers communicated in various ways. For example, those with profound aphasia can often provide accurate and reliable answers to yes and no questions when confronted by a sensitive and skilled interviewer. For these patients it is important to be creative in establishing communication methods for the purpose of pain assessment.

Although pain is an individual experience, the use of family and caregivers in the assessment of pain can sometimes be helpful. Among patients with cognitive impairment, the history is often only obtainable from family or close caregivers. Family and caregivers are an excellent source of qualitative information about general behavior, medication usage, actions that seem to reduce pain and actions that seem to aggravate pain. It is important to remember, however, that family and caregivers are limited in their interpretation of events and behaviors. In fact, evidence has suggested that when it comes to estimating pain intensity, proxies are not always very accurate or reliable. Our studies of elderly cancer patients suggest that caregivers may overestimate pain intensity and distress. It is often distressing to family and other caregivers who feel helpless in managing severe pain. Both physicians and nurses have been found to underestimate pain as well as provide inadequate pain medication. In the final analysis, family and close caregivers can be valuable sources of qualitative information, but they probably should not be relied on entirely for quantitative assessment of pain intensity or distress, especially among those patients who are able to communicate their pain experiences.

MANAGEMENT OF ACUTE AND PERIOPERATIVE PAIN

The treatment of acute pain relies largely on short-term use of analgesic medications and resolution of the underlying cause. A variety of non-drug strategies have also been shown to be helpful. The choice of analgesic medications and other strategies may depend on the severity of pain, availability of technical equipment and expertise, expectations for resolution of underlying injury, and individual patient characteristics.

The most common approach to treating acute pain is based on the World Health Organization’s recommendations for choosing the potency of analgesic drugs based on the intensity of pain. Pain of mild intensity usually responds to non-opioid drugs used alone or in combination with other physical and cognitive-behavioral interventions. Pain of moderate intensity often requires more intensive efforts, such as weak opioids or low doses of more potent opioid drugs. Many of these drugs are compounded with NSAIDs or acetaminophen to achieve enhanced relief with only modest exposure to the risk and side-effects of many potent opioids. Severe pain usually requires potent opioid analgesic medications given alone or in combination with other analgesic strategies. For severe trauma or post-operative pain, intermittent intravenous, continuous intravenous, or spinal anesthesia may provide faster and more continuous pain relief. Finally, when patients present with acute pain, even though establishing a diagnosis is a priority, symptomatic pain treatment should not be held while investigations are proceeding. It is rarely justified to defer analgesia until a diagnosis is made. In fact, a comfortable patient is better able to cooperate with diagnostic procedures.

Acute and post-operative pain is dynamic. Without treatment, sensory input from damaged tissue causes alterations in spinal cord neurons that result in enhanced responses. Pain receptors also become more sensitive after injury. Studies have demonstrated long lasting changes after brief, painful stimuli. These observations may explain why long standing pain is more difficult to suppress. Thus, patients should be encouraged to take pain medications continuously or to prevent pain before it becomes severe and requires higher doses of medication suppress. In general, it may be helpful to provide continuous analgesics initially, with intermittent or "PRN" doses reserved for breakthrough or intermittent pain as the injury resolves.

Aggressive pain prevention and control before, during, and after surgery can have both short- and long-term benefits. Good pre-operative pain control has been shown to make post-operative pain easier to control. Post-operative patients who use analgesia via a continuous infusion pump with self-administered boluses for breakthrough pain report less pain and are more satisfied with their pain control. These patients use less medication, have fewer post-operative complications, and tend to be discharged earlier compared to similar patients who are given similar drugs on an intermittent or "as needed" basis.

The importance of pre-operative patient education cannot be overemphasized. Studies have shown that pre-operative patient education and preparation dramatically enhances post-operative outcomes and improved pain management. Patients given complete information about specific procedures including detailed descriptions of expected discomfort post-operatively often have less pain, use less pain medication, and have earlier discharges.

MANAGEMENT OF PERSISTENT PAIN

The management of persistent pain often requires a multimodal approach of drug and non-drug pain management strategies. Although analgesic medications are the most common strategy employed, the concurrent use of cognitive-behavior therapy and other non-drug strategies may be essential to reduce long-term reliance on medications alone, which have substantial side effects when used on a long-term basis.

It is important to consider that persistent pain management is often a labor-intensive effort. Not unlike the effort required during warfarin anticoagulation, pain management requires frequent monitoring and, usually, adjustments. Indeed, elderly patients with persistent pain benefit particularly from physicians, nurses, and restorative personnel who are able to employ an interdisciplinary approach to complex problems.

In general, persistent pain is more difficult to relieve than acute pain. Patients should be given an expectation of pain relief, but it is unrealistic to suggest or sustain an expectation of complete relief for some patients with persistent pain. The goals and trade-offs of possible therapies need to be discussed openly. Sometimes a period of trial-and-error should be anticipated when new medications are initiated and titration occurs. Review of medications, doses, use patterns, efficacy, and adverse effects should be a regular process of care. Ineffective drugs should be tapered and discontinued.

Economic issues are also important in the management of persistent pain. It is appropriate to consider economic issues and make balanced decisions while basic principles of assessment and treatment are followed. Healthcare professionals should be aware of the costs and economic barriers patients and families may encounter with the strategies often prescribed. These issues include lack of Medicare reimbursement for some strategies, limited formularies, delays in referrals in some managed care environments, delays from mail-ordered pharmacies, and limited availability of strong opioid medications in some pharmacies.

ANALGESIC MEDICATIONS

Any patient who has pain that impairs functional status or quality of life is a candidate for analgesic drug therapy. Analgesic medications are safe and effective in elderly people, but they carry a balance of benefits and burdens. For some classes of pain-relieving medications, opioids, for example, elderly patients have been shown to have increased analgesic sensitivity. However, elderly people are a heterogeneous population, thus optimum dosage and known side effects are difficult to predict.

Recommendations for age-adjusted dosing are not available for most analgesics. In reality, dosing for most patients requires beginning with low doses with careful upward titration, including frequent re-assessment for dosage adjustments and optimum pain relief.

The least invasive route of drug administration should be used. Some drugs can be administered from a variety of routes such as subcutaneous, intravenous, transcutaneous, sublingual, and rectal. Most drugs are limited to only a few safe routes of administration, but new delivery systems are being created each year. The oral route is preferable because of its convenience and relatively steady blood levels produced. Significant drug effects are often seen in 30-minutes-to-2-hours for most analgesics given orally, which may be a drawback in acute, rapidly fluctuating pain. Intravenous bolus provides the most rapid onset and shortest duration of action, which may require substantial labor, technical skill, and monitoring. Subcutaneous and intramuscular injections, although commonly used, have disadvantages of wider fluctuations in absorption and rapid fall off of action compared to oral routes. Transcutaneous, rectal, and sublingual routes are also more difficult to predict, but may be essential for those for whom swallowing is difficult.

Timing of medications is also important. Fast-onset, short-acting analgesic drugs should be used for episodic pain. Medications for intermittent or episodic pain can usually be prescribed as needed (PRN). For continuous pain, medications should be provided around the clock. In these situations, a steady state analgesic blood level is more effective in maintaining comfort. Most patients with continuous pain also need fast-onset, short-acting drugs for breakthrough pain. Breakthrough pain includes: 1) end-of-dose failure as the result of decreased blood levels of analgesic with concomitant increase in pain prior to the next scheduled dose; 2) incident pain, usually caused by activity that can be anticipated and pre-treated; and 3) spontaneous pain, common with neuropathic pain that is often fleeting and difficult to predict.

The use of placebos is unethical in clinical practice, and there is no place for their use in the management of acute or persistent pain. Placebos, in the form of inert oral medications, sham injections, or other fraudulent procedures are only justified in certain research designs where patients have given informed consent and understand that they may be receiving a placebo as a part of the research design. In research, placebos help identify and measure random or uncontrollable events that may confound results of some research designs. In clinical settings, placebo effects are common, but they are neither diagnostic of pain nor indicative of a therapeutic response. The effects of placebos are short lived and most patients eventually learn the truth resulting in loss of patient trust and more needless suffering.

Acetaminophen
Acetaminophen is the drug of choice for elderly adults with mild-to-moderate pain, especially if the pain is caused by osteoarthritis and other musculoskeletal problems. As an analgesic and anti-pyretic, acetaminophen acts in the central nervous system to reduce pain perception. Although it may have some minor drug interactions (e.g. warfarin), given in a dose of 650mg to 1000mg four times a day, it remains the safest analgesic medication compared to traditional NSAIDs and other analgesic drugs for most patients. Unfortunately, acetaminophen overdose can result in irreversible hepatic necrosis. Therefore, the maximum daily dose should never exceed 4000mg per day.

Non-steroidal Anti-inflammatory Drugs
Non-steroidal Anti-inflammatory Drugs (NSAIDs) have peripheral and central analgesic activity. They are potent inhibitors of prostaglandin synthesis, which have effects on inflammation, pain receptors, and nerve conduction, and may have central effects as well. There are two major NSAID-sensitive cyclo-oxigenase enzymes (COX-1 and COX-2) synthesized in a variety of organs. COX-1 is present in most organ systems and plays a role in normal organ function, such as gastric mucosal blood flow and barrier function, renal blood flow, hepatic blood flow, and platelet aggregation. COX-2, normally present in lower concentrations, is an inducible enzyme in response to injury or inflammation. Selective inhibition of COX-2 gives rise to analgesic and anti-inflammatory activity with less organ toxicity compared to the non-selective inhibition both enzymes. Clinical trials have found COX-2 inhibitors to be similarly effective to traditional NSAIDs in terms of peak pain relief, total pain relief, and in indices of joint inflammation in patients with arthritis. Safety profiles of these agents have shown a 50% reduction of gastrointestinal injury when used alone, but little data is available to support additional gastrointestinal injury with concomitant use of proton pump inhibitors or mesoprostyl. On the other hand, patients taking some COX-2-specific inhibitors (specifically roficoxib) may have an increased risk for cardiovascular events. Thus, patients at risk for cardiovascular events who are taking COX-2-specific NSAIDs should also consider low dose aspirin to offset this effect. Unfortunately, the COX-2 drugs remain expensive and the cost-benefit ratio remains controversial.

Non-specific inhibitors of COX enzymes (older NSAIDs) are still appropriate for short-term use in inflammatory arthritic conditions, such as gout, calcium pyrophosphate arthropathy, acute flare ups of rheumatoid arthritis, and other inflammatory rheumatic conditions. They have also been reported to relieve the pain of headache, menstrual cramps, and other mild-to-moderate pain syndromes. These drugs can be used alone for mild-to-moderate pain, or in combination with opioids for more severe pain. They have the advantage of being non-habit forming. Individual drugs in this class vary widely with respect to anti-inflammatory activity, potency, analgesic properties, metabolism, excretion, and side effect profiles. Moreover, it has been observed that failure of response to one NSAID may not predict the response to another.

A disadvantage of NSAIDs, including COX-2 specific inhibitors, is that they all demonstrate a ceiling effect, that is, a level at which increasing doses provides no further increase in analgesia. A large number of NSAIDs are now available; however, there is no evidence to support a particular compound as the NSAID of choice. Several are available over-the-counter without a prescription. Table 4 lists COX-2 and other selected NSAIDs for pain.

High dose NSAIDs for long periods of time should be avoided in elderly patients. Of major concern is the high incidence of adverse reactions, including gastrointestinal bleeding, renal impairment, and bleeding diathesis from platelet dysfunction. The concomitant use of mesoprostyl, histamine-2 receptor antagonists, proton pump inhibitors, and antacids is only partially successful at reducing the risk of significant gastrointestinal bleeding associated with NSAID use. Also, the side effect profiles of gastro-protective drugs in this population must be weighed against their limited benefits. These gastro-protective medications do nothing to prevent renal impairment and other side effects. For those with multiple medical problems, NSAIDs are associated with increased risk of drug-drug and drug-disease interactions. NSAIDs may also interact with anti-hypertensive therapy. Thus, the relative risks and benefits of NSAIDs must be weighed carefully against other available treatments for older patients with persistent pain problems. For some patients, long-term opioid therapy, low-dose or intermittent corticosteroid therapy, or many other non-opioid analgesic drug strategies may have fewer life threatening risks compared to long-term, high dose NSAID use.

(Figure 4)

Opioid Analgesic Medications
Opioid analgesic medications act by blocking receptors in the central nervous system (brain and spinal cord) resulting in a decreased perception of pain. Many opioids act similarly to local anesthetics and have recently found widespread use in epidural anesthesia. Selected opioid analgesic medications are listed in Table 5. Opioid drugs have no ceiling to their analgesic effects and have been shown to relieve all types of pain. Advanced age is associated with a prolonged half-life and prolonged pharmacokinetics of many opioid drugs. Thus, elderly people may achieve pain relief from smaller doses of opiate drugs than younger people.

(Figure 5)

Opioid drugs have the potential to cause cognitive disturbances, respiratory depression, constipation, and habituation in older people. Drowsiness, performance-based measures of cognitive impairment, and respiratory depression associated with opioids should be anticipated when opioids are initiated and doses are escalated rapidly. Drowsiness, cognitive impairment, and respiratory depression occur in a dose dependent fashion and can be used to judge dose escalations. If patients have unrelieved pain with little drowsiness or cognitive impairment, doses may be safely escalated. Tolerance usually develops in a few days to these side effects at which time patients usually return to a fully alert status and baseline cognitive function. Until tolerance develops, patients should be instructed not to drive and to take precautions against falls or other accidents. Once tolerance to these effects has developed, patients can return to normal activities including driving and other demanding tasks despite high doses of opioid drugs. In fact, cancer patients are often observed to have improved physical functioning once pain is adequately relieved on opioid analgesics.

Constipation is a side effect of opioid drugs to which older patients do not develop tolerance. The management of constipation usually includes increasing fluid intake, maintaining mobility, and using cathartic medications. Some patients find relief with remedies like prune juice or other natural laxatives. Other patients may require more potent osmotic laxatives such as milk of magnesia, lactolose, or sorbitol. But for many patients, opioid-induced constipation may require potent stimulant laxatives such as senna or biscodyl. It should be remembered that stimulants should not be used until impactions have been removed and obstruction has been ruled out. Finally, some patients require regular enemas to ensure bowel evacuation during high dose opioid administration for severe pain.

Nausea also occasionally complicates opioid therapy. Nausea from opioid medications may result from several mechanisms and may wane as tolerance develops. Traditionally, anti-emetics such as prochlorperazine, chlorpromazine, and antihistamines have been the mainstay of treatment for nausea in younger patients. Low dose haloperidol (Haladol) has also been used, anecdotally noting a lower side effect profile compared to other neuroleptic drugs. Remember that all of these agents have high side effect profiles in elderly patients, including movement disorders, delirium, and anticholinergic effects. Thus, clinicians should choose anti-emetic medications with the lowest side effects and continue to monitor patients frequently.

Tolerance is a pharmacologic phenomenon that occurs with many drugs. Tolerance is defined by diminished effect of a drug associated with constant exposure to the drug over time. For opioid drugs, tolerance is difficult to predict. In general, tolerance to drowsiness and respiratory depression occur much faster than tolerance to analgesic properties of the drug. Previous reports that described tolerance among cancer patients resulting in the need for massive doses of morphine to achieve adequate analgesic were probably misinterpreted because those patients also had rapidly advancing cancer. More recent studies of opioid-managed arthritis pain noted that tolerance was not often significant. In fact, some patients have been noted to remain on stable doses of opioids for many years without demonstrating significant tolerance to the analgesic effects.

Dependency is also a pharmacologic phenomenon associated with many drugs including for example corticosteroids and beta blockers. Dependency is present when patients experience uncomfortable side effects when the drug is withheld abruptly. Drug dependence requires constant exposure to the drug for some period of time, but it is difficult to predict. The minimum dose and time relationship between drug exposure and development of dependent withdrawal symptoms is not precisely known, but it appears to vary with individual opioid compounds. Symptoms associated with opioid withdrawal may include anorexia, nausea, diaphoresis, tachycardia, mild hypertension, and mild fever. Worsening symptoms may include skin mottling, gooseflesh, and frank autonomic crisis. Fortunately, these symptoms can be ameliorated easily by tapering opioids over a few days. In severe cases, clonidine given short term in titrated doses will usually control serious autonomic signs. It is important to remember that physiologic effects of opioid withdrawal are usually not life threatening compared to withdrawal of alcohol, benzodiazepine, or barbiturates.

Addiction is a behavioral problem and is defined in such terms. Addictive behavior is defined by compulsive drug use despite negative physical and social consequences, and the craving for effects other than pain relief. Addicted patients often have erratic behavior that can be observed in a clinical setting in the form of selling, buying, and procuring drugs on the street, and the use of medication by bizarre means such as dissolving tablets for self IV administration.

It is now known that drug use alone is not the major factor in the development of addiction. Other medical, social, and economic factors play immense roles in addictive behavior. It is also important to not construe certain behaviors as necessarily addictive behaviors. Hording of medications, persistent or worsening pain complaints, frequent office visits, requests for dose escalations, and other behaviors associated with unrelieved pain has coined the term ”pseudo-addiction." Laws, regulations, and unintentional behavior by prescribing clinicians may require patients to hoard medication and seek other physicians for additional help. In fact, true addiction is rare among patients taking opioid analgesic medications for medical reasons. This is not meant to imply that opioid drugs can be used indiscriminately, only that physician fears of addiction and side effects do not justify the failure to treat pain in elderly patients, especially those near the end-of-life.

Other Non-opioid Medications for Pain
A variety of other medications not formally classified as analgesics have been found to be helpful in certain specific pain problems. The term "adjuvant analgesic drugs," although frequently used, is a misnomer in that some of these non-opioid drugs may be the primary pain relieving pharmacologic intervention in certain cases. Table 6 provides some examples of non-opioid drugs that may help certain kinds of pain.

The largest body of evidence available relates to the use of these drugs for neuropathic pain, such as diabetic neuropathies, postherpetic neuralgia, and trigeminal neuralgia. Tricyclic antidepressants, anticonvulsants, and local anesthetics are the most frequently used non-opioid analgesics for neuropathic conditions. In general, these drugs have had limited success in pain syndromes that are not associated with neuropathic mechanisms. Most reports have found that these agents are only partially successful. Typically, about 50-70% of patients have a measurable response and of those, most only experience partial relief. Thus, these drugs are often not panaceas and are rarely totally successful as single agents. One exception may be with trigeminal neuralgia where carbamazepine is probably the drug of choice. Usually these agents work better in combination with other traditional drug and non-drug strategies in an effort to improve pain and keep other drug doses to a minimum. Failure of response to one particular class of drugs does not necessarily predict failure of another class of agents. In general, non-opioid medications for neuropathic pain should be chosen according to lowest side effects. Treatment should usually start with lower doses than recommended for younger patients, and doses should be escalated slowly based on known pharmacokinetics of individual drugs and appropriate knowledge of disease-specific treatment strategies. Unfortunately, most of the non-opioid medications for pain management have high side effect profiles in the elderly. Thus, these medications often have to be monitored carefully.

(Figure 6)

Antidepressants have been the most widely studied class of non-opioid medication for pain. The mechanism of action for these drugs is not entirely known, but probably has to do with interruption of norepinephrine and serotonin mediated mechanisms in the brain. For neuropathic pain, the major effect of these drugs is not their mood altering capacity, although this may also be helpful in those with concurrent major depression. More is probably known about tricyclic antidepressants than the other subclasses. A randomized, placebo-controlled trial of amitriptyline, desimipramine, and fluoxetine indicated that desimipramine may be as effective as amitriptyline, but fluoxetine is no better than a placebo for the treatment of diabetic neuropathy. Thus, desimipramine may be a better choice because it has a lower side effect profile in elderly people than amitriptyline. Unfortunately, tricyclic antidepressants have been criticized for high anticholinergic side effects in the elderly patients, which often limits there effectiveness.

The newer norepinephrine reuptake inhibitors (SNRIs) including venlafaxine (Effexor) and duloxetine (Cymbalta) have been shown to have modest effect on diabetic neuralgia, and duloxetine is FDA-approved for use in diabetic neuropathy. Pain studies on these drugs have indicated small effect sizes, but statistically significant.

Studies of the serotonin re-uptake inhibitors (SSRIs), which may have lower side effect profiles for elderly people, have not been shown effective for pain management. In fact, none have shown significant effect on pain despite being highly effective for depression.

For many years, it has been known that some medications with anti-epileptic activity may relieve the pain of trigeminal neuralgia (Tic Douloureux). Studies have shown that compounds such as dilantin, tegretol, and valproic acid may also help diabetic neuralgia and other neuropathic pains in some patients. In general, the usefulness of these drugs has been limited by their high side effect profiles in elderly people and the fact that most patients respond only partially, making the overall risk/benefit ratio rather large in this population. Indeed, these drugs are not simple analgesics and should not be used for the relief of trivial aches and pains. Of recent interest has been the effectiveness of gabapentin for treatment of diabetic neuralgia and postherpetic neuralgia. Clinical observations suggest that this agent has a significant analgesic effect on neuropathic pain with a much lower side effect profile compared to other anti-epileptic drugs and most antidepressants as well.

Several local anesthetics have also been shown to relieve neuropathic pain when administrated systemically in addition to their known local anesthetic effects. Intravenous lidocaine has been found to sometimes predict the response to other anticonvulsants and systemically administered local anesthetics. Mexilitine (Mexil), similar to lidocaine but active orally, has also shown some activity against the neuropathic pain of diabetic neuralgia. Although this drug also has a high risk/benefit ratio, some studies have reported response rates at lower doses than are often recommended for cardiac arrhythmias.

Finally, persistent pain associated with osteoporosis has often been shown to improve with calcitonin. Most investigations of the effects of calcitonin on osteoporosis have reported anecdotally that pain improves significantly. These studies have not been designed as pain studies and more sophisticated assessment of pain in these studies would be welcome, but results thus far are encouraging.

ANESTHETIC AND NEUROSURGICAL APPROACHES TO PAIN MANAGEMENT

A wide variety of anesthetic and neurosurgical approaches to pain are available and some require highly specialized skills. Although it is beyond the scope of this chapter to review details of all of these techniques, a few deserve mention.

Trigger point injections have been used extensively for the treatment of myofascial pain syndromes. Myofascial pain with trigger points was first recognized more than 50 years ago. In a relatively high percentage of cases, trigger points may initiate a reflex mechanism that produces referred pain, tenderness, and muscle spasm. With local injection of the trigger point followed by stretching and reconditioning of the muscles, the myofascial pain syndrome usually subsides. More recently, similar results have been obtained using ice massage or vapocoolent spray applied topically followed by specific muscle stretching and physical therapy techniques. Nonetheless, trigger point injections with diluted local anesthetics may be highly effective when combined with specific physical therapy for many myofascial pain syndromes.

Continuous drug infusions are highly effective for providing steady state analgesic drug levels. Continuous infusions can be maintained by implantable pumps or external devices to deliver intravenous, subcutaneous, intrathecal, or epidural medications. Continuous infusions of opioid drugs have found widespread use in severe persistent cancer pain, especially among those near the end of life. Other uses have included continuous infusion of muscle relaxants for patients with severe muscle spasms from spinal injury, multiple sclerosis, or end-stage Parkinson’s disease. Whether these invasive high tech strategies are appropriate for patients with all kinds of persistent pain remains controversial. These techniques are very expensive, but are often reimbursed by third party payers, including Medicare. These issues have raised ethical issues about the application of high tech strategies for patients who might be equally well-managed using oral medications that are not reimbursable. In general, these interventional methods should be used only when oral medications become ineffective or the oral route of administration is no longer viable. More work needs to be done to justify these risky and expensive techniques that need to be carefully monitored in nursing homes, home care, and other low tech long-term care settings.

NON-DRUG STRATEGIES FOR PAIN MANAGEMENT

Non-drug strategies, used alone or in combination with appropriate analgesic medications, should be an integral part of the care plan for most elderly patients with significant pain problems. Non-drug strategies for pain management encompass a broad range of treatments and physical modalities, many of which carry low risks for adverse effects. Used in combination with appropriate drug regimens, these interventions often enhance therapeutic effects while allowing medication doses to be kept low to prevent adverse drug effects.

Among the non-drug interventions, the importance of patient education cannot be overstated. Studies have shown that patient education programs alone significantly improve overall pain management. Such programs often include content about the nature of the pain, how to use pain diaries and pain assessment instruments, how to use medications appropriately, and how to use self-help, non-drug strategies. Whether conducted in groups or individually, education should be tailored for individual patient needs and level of understanding. Written materials and methods of reinforcement are important to the overall success of the program.

Physical exercise is important for most patients with pain. A program of exercise can be tailored to most patients’ needs, and is extremely important for rehabilitation and the maintenance of strength and endurance. Clinical trials of older patients with persistent musculoskeletal pain have shown that moderate levels of exercise (aerobic and resistance training) on a regular basis are effective in improving pain and functional status. Initial training for persistent pain patients usually requires 8-12 weeks with supervision by a professional who can focus on the needs of older people with musculoskeletal disorders. There is no evidence that one form of exercise is better than another, so programs can be tailored for the individual's needs, lifestyle, and preference. The intensity of exercise along with frequency and duration must be adjusted to avoid exacerbation of the underlying condition while gradually increasing and later maintaining overall conditioning. It is important to remember that feeling better often gives rise to a false impression that the discipline of regular exercise is not necessary. Continued encouragement and reinforcement is often required. Unless complications arise, the program of exercise should be maintained indefinitely to prevent deconditioning and deterioration.

Psychological strategies have been shown to be helpful for some people with significant pain. Cognitive therapies are strategies aimed at altering belief systems and attitudes about pain and suffering. Cognitive therapies include various forms of distraction, relaxation, biofeedback, and hypnosis. Behavioral therapies are strategies aimed at enhancing healthy behaviors and discouraging abnormal behavior that is unpredictable and self-defeating. Cognitive therapy can be combined with behavioral approaches, and together they are known as cognitive-behavioral therapy. Cognitive-behavioral therapy in its purest form includes a structured approach to teaching coping skills that might be used alone or in combination with analgesic medications and other non-drug strategies for pain control. Effective programs can be conducted by trained professionals with individual patients or in groups, and there is some evidence that the effect is enhanced with caregiver involvement. Although it may not be appropriate for those with significant cognitive impairment, there is evidence from randomized trials to support the use of cognitive-behavioral therapy for many patients with significant persistent pain.

Finally, a variety of alternative therapies are also used by many patients. Many patients seek alternative medicine approaches with and without the knowledge or recommendation of their physician or other primary care provider. Alternative medicine approaches to persistent pain may include homeopathy, spiritual healing, or the growing market of vitamin, herbal, and natural remedies. Although there is little scientific evidence to support these strategies for pain control, it is important that healthcare providers not abandon patients or leave them with a sense of hopelessness.

RECOMMENDED READINGS:
  1. AGS Panel on Persistent Pain in Older Persons: The management of persistent pain in older persons. Journal of the American Geriatrics Society, 50(5):205-224, 2002.
  2. Hadjistavropoulos T, Herr K, Turk DC, Fine PG, Dworkin RH, Helme R, Jackson K, Parmelee PA, Rudy TE, Lynn Beattie B, Chibnall JT, Craig KD, Ferrell B, Ferrell B, Fillingim RB, Gagliese L, Gallagher R, Gibson SJ, Harrison EL, Katz B, Keefe FJ, Lieber SJ, Lussier D, Schmader KE, Tait RC, Weiner DK, Williams J: An interdisciplinary expert consensus statement on assessment of pain in older persons. Clin J Pain. 2007 Jan; 23(1 Suppl):S1-43.
  3. Cancer Pain Management Guideline Panel: The Management of Cancer Pain in Adults and Children, The American Pain Society, 2005.
  4. Arthritis Pain Guideline Panel: Guideline for the Management of Pain in Osteoarthritis, Rheumatoid Arthritis and Juvenile Chronic Arthritis. The American Pain Society, 2002
  5. Pain in Older Persons. Stephen J. Gibson and Debra K. Weiner (Eds), IASP Press, Seattle, 2002.
  6. Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain, 5th Edition. The American Pain Society, 2003.
  7. Ferrell BA, Whiteman JE: Pain, in Geriatric Palliative Care. Morrison RS, Meier DE (Eds) Oxford University Press, New York, 2003, pp 205-229.
  8. Dionne CE, Dunn KM, Croft PR: Does back pain prevalence really decrease with increasing age? A systematic review. Age and Aging 35:229-234, 2006.
  9. Barkin RL, Barkin SJ, Barkin D: Propoxyphene (dextroproposyphene): A critical review of a weak opioid analgesic that should remain in antiquity. American Journal of Therapeutics 13:534-542, 2006.
  10. Kuffner EK, Dart RC, Bogdan GM, et al: Effect of maximal daily doses of acetaminophen on the liver of alcoholic patients. Archives of Internal Medicine 161:2247-2252, 2001.
  11. Mahe I, Bertrand N, Drouet L, et al: Interaction between paracetamol and warfarin in patients: A double blind, placebo-controlled randomized trial. Haematologica 91:1621-1627, 2006.
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