GERIATRIC PAIN MANAGEMENT

GERIATRIC ANESTHESIA

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GERIATRIC PAIN MANAGEMENT The Anesthesiologist’s Perspective Gordon M. Freedman, MD, and Ramani Peruvemba, MD

When we were doing our Anesthesiology residencies, the pediatric anesthesiologists constantly emphasized that “kids are not just small adults.” So too, geriatric patients are not just ”old adults.” There are differences in physiology and subsequent pharmacokinetic and pharmacodynamic properties that affect many aspects of managing geriatric pain. The definition of a geriatric patient is a constantly changing concept. What was old 50 years ago might be considered middle age today. If you subscribe to the somewhat arbitrary cutoff that geriatrics begins at 65 years of age, then this population constitutes approximately 12% of the overall population of the United States in the 1990s compared with 4% in 1900. By the year 2030, people over 65 years old are projected to make up approximately 17% of the population9l With ever improving medical and nutritional conditioning for people of all ages, a more important concept is physiologic age as opposed to chronologic age. Rowe and Kahn coined the terms successful aging and usual aging to correlate the process of advancement in age to a physiologic reference point. Successful aging occurs with minimal physiologic deterioration.lZ2 PHYSIOLOGIC EFFECTS OF AGING

When discussing pain management in geriatric patients, one must consider the physiology of aging and its effects on the clinical aspects of the analgesic interventions. Cardiac index, on the average, can decrease approximately 1% per year after the age of 30.39Any medications given intravenously will have a slower circulation time and a longer onset to effect. Pulmonary function is

From the Department of Anesthesiology, Mount Sinai School of Medicine (GMF); and Mount Sinai Pain Management Service (GMF), Department of Anesthesiology (RP), Mount Sinai Medical Center, New York, New York

ANESTHESIOLOGY CLINICS OF NORTH AMERICA VOLUME 18 * NUMBER 1 * MARCH 2000

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reduced in the elderly and the clinical implications of respiratory depression take on added importance.lW,lZ7 Renal function decreases approximately 1%per year. This is owing to a decrease in the number and function of glomeruli, along with a decrease in renal blood flow secondary to a decrease in cardiac Hepatic blood flow, tissue mass, and microsomal enzyme function are also all decreased with age.133 Because of the age-related impaired function of the two main organs for metabolism, excretion and elimination, the duration of action of most analgesics will be prolonged in older patients. All analgesics when circulating throughout the body are protein bound. A decrease in protein binding will allow medications to pass through membranes like the blood-brain barrier more easily and have an increased effect on the central nervous system. With age there is a decrease in both the amount of some circulating proteins and the functional effectiveness to bind.6 Add to this the coadministration of the polypharmacy associated with aging that can lead to displacement of pain medications from binding sites on the proteins, and the overall outcome is an exaggerated analgesic effect. Body habitus changes that occur with age are associated with a loss of total body water and a reduction in blood v0lume.9~ Intravenously injected medications will give higher plasma drug concentrations and again an exaggerated response to analgesics. It is not uncommon to find a gradual cognitive decline with aging. This may be associated with multiple central nervous system degenerative disease processes such as Alzheimer's disease or cerebral atherosclerotic disease. The aging brain, for many of the pharmacokinetic reasons previously mentioned, is more susceptible to the analgesic effects of pain medications. Pharmacodynamic effects also are important to the analgesic sensitivity of the elderly. Both cortical and subcortical areas of the brain atrophy with age. Along with this there is both a decrease in receptor sites and affinity and a decrease in the synthesis of neurotransmitters. All of these factors make analgesics more potent in the elderly. In the peripheral nervous system, aging is associated with a decrease in nerve conduction velocity. This may be owing to axonal loss of myelin or a decrease in axon number and synapses.34 GERIATRIC PAIN

The prevalence of geriatric pain in the general population is controversial. Crook et a1 looked at 500 randomly selected households from a Canadian family practice clinic and showed a twofold increase in reported pain complaints in patients over 60 years of age as compared with patients under 60.21Conversely, Brattberg et a1 in a Swedish postal survey study showed the age group with the highest prevalence of chronic pain to be 45 to 64 (50%).The age group 65 to 84 reported 36.1% chronic pain problems.l0 In the nursing home environment, functionally impairing pain has been shown to affect from 45% to 80% of residents.&In a nursing home study by Ferrell et al, 71% of residents had at least one pain complaint and 51% described pain on a daily basis.46The most common causes of geriatric pain are lower back pain, osteoarthritis, previous fractures, and neuropathie~.'~~ Corran et a1 attempted to classify chronic pain in relation to age.19 They found that the classic patient profile for chronic pain consisting of high pain, high functional impact and high mood disturbance identified in younger and middle-aged adults does not occur as frequently in older patients. A different

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profile emerged in the older patients called the high-impact group. It manifested as high functional impact and depression with low levels of pain. Even low pain can be a significant psychologic and physical burden to an elderly person. The effect of age on pain perception has been one of the most controversial topics related to geriatric pain. The question is clouded owing to a lack of uniformity regarding methods, stimuli, and endpoints. There are studies indicating increases, decreases, and no change in pain sensitivity with increasing age.2o, 59, 135 Psychocultural aspects can also bias pain reporting.60 Pain itself is not a homogeneous entity, and older persons might have increased tolerance to cutaneous pain but decreased tolerance to deep pain.146An anatomic correlate was published in 1996 showing that elderly adults rely predominantly on C-fiber input when reporting pain whereas younger adults use additional input from A[delta] fibers.15 In the past, because of a perceived lack of sensitivity to pain in the elderly, geriatric pain was not aggressively treated. Subsequently, many studies have documented the importance of treating chronic pain in the elderly in both outpatient pain management centers and home hospice-type 24, 93 In the nursing home setting, the validity of treating pain even in the cognitively lo7 Assessment of pain becomes impaired residents has also been do~umented.'"~, a major problem, especially in patients with impaired lZ6The use of one of several unidimensional pain intensity scales (e.g., McGill Pain Questionnaire, Present Pain Intensity Subscale, or the Rand Coop Chart) proved to be successful for assessing patients with mild to moderate cognitive impairment." Depression is a frequent accompaniment to chronic pain.14Depressed elderly individuals have been shown to be more likely to report pain.lo6As opposed to young chronic pain patients, there is a strong association between pain severity and depression in older patients.136Coping mechanisms do seem to remain intact in elderly chronic pain patients.74,75 Pain and depression are common in patients with cancer. Educational, supportive, and palliative care for these patients is important both in the home and the hospital.8,48, 77 A study by Moss et a1 looked at the role of pain in the last year of life of older persons. They found that pain increased over the final year. One month before death, 66% felt pain freq~ently.~~ 42z

CLINICAL GERIATRIC PAIN MANAGEMENT

Geriatric pain management is one of the most underused subspecialties in medicine. Out of 4000 Medline papers published on pain per year, less than 1% are related to pain management in the Of these, virtually none promote the anesthesiologist's input into this important topic. The object of this section is to review the more common chronic pain problems in geriatric patients and to focus on the different analgesic regimens available and the advantages as they relate to the geriatric population. Chronic pain has been variously defined depending on the literature that you read. Some define chronic pain as any pain associated with a recurrent or chronic process. Some arbitrarily define chronic pain as any pain that persists for 6 months or more. The seemingly most clinically relevant definition defines chronic pain as pain that persists for approximately 1 month beyond the acute disease or a reasonable time for healing.

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Osteoarthritis

Forty million Americans have radiologic evidence of degenerative joint disease. Of patients over 70 years of age, 85% have some findings.84The prevalence of osteoarthritis increases with age,139with large increases after age 50 in men, and after age 40 in women.8O The prevalence of symptomatic osteoarthritis varies depending on the anatomic site. In the hands, the prevalence in a community-based population is 2% to 4% and 30% to 71% in a clinic base. The prevalence of symptomatic osteoarthritis of the knee is 10%to 30% in the elderly compared with 1%in the h1ps.8~ Although osteoarthritis is more prevalent in the aged, is this owing to a disease state or the natural progression of aging? Evidence supports osteoarthritis as a pathologic entity. Denatured type I1 collagen is found in both normal aging and cartilage from patients with osteoarthritis; but in the latter, the finding is more extensive.@Differences also can be found in the organic makeup of the cartilage regarding the ratio of chondroitin sulfate to keratin sulfate.lloGenetic markers that are found only in fetal or neonatal cartilage can be found in osteoarthritic cartilage, differentiating it from normal aging ~artilage.8~ The clinical diagnosis of osteoarthritis is made by history and physical examination along with radiographic findings. Laboratory tests are not helpful in making this diagnosis. The chief complaint is pain, especially in motion and weight-bearing joints. The pain is described as achey and is associated with joint stiffness that occurs after resting and subsides upon resumption of motion. On physical examination, there is decreased range of motion, local tenderness, bony enlargement, small effusions, and crepitus. Erythema and heat over the joint are unusual. Currently, there are not therapeutic regimens available to treat the underlying pathology of osteoarthritis. Treatment management consists of modalities mainly to relieve pain and improve functional incapacitation. Management modalities include nonpharmacologic, pharmacologic, and interventional. A randomized trial of frail nursing home residents showed that a standardized physical therapy program can provide mobility benefits for people with physical disability owing to multiple comorbid conditions including osteoarthritis.96Behavior modification has also been demonstrated in elderly nursing home residents to decrease as-needed (PRN) pain medications, pain behaviors, and subjective reports of ~ a i n . 9Transcutaneous ~ electrical nerve stimulation (TENS) has been recommended for use in the elderly for many painful syndromes, including osteoarthritis.134 These nonpharmacologic modalities provide the geriatric patient with the optimal situation of decreasing pain with minimal side effects. The most common medications used to treat the pain of osteoarthritis include acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs). Acetaminophen has been shown to be equivalent to the NSAIDs in treating the short-term pain of osteoarthritis of the knee. In doses up to 4000 mg/d, acetaminophen is considered by some, owing to the low incidence of side effects, to be the analgesic of choice for osteoarthritis in the elderly. NSAIDs, although also first-line analgesics for osteoarthritis, have been associated with a high incidence of gastrointestinal ulceration and bleeding in the elderly owing to their nonspecific inhibition of cyclooxygenase (COX)?7In addition, these medications may cause impairment of renal function in the aged (manifested as an increase in serum blood urea nitrogen [BUN] and creatinine levels), particularly in those patients with marginal preexisting function.58Cyclooxygenase-2 (COX2) inhibitors are presently being developed to try to improve the side effects profile of the NSAIDs. They more selectively inhibit COX-2 enzymes and rela-

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tively maintain the protective prostaglandin effect on the stomach and kidneys of the COX-1 enzyme. This class of drugs promises to provide an exciting alternative analgesic with reduced amounts of complications. The use of opioids for treatment of nonmalignant pain is controversial, and even more so in the elderly. Portenoy and Foley retrospectively studied patients up to the age of 82 with multiple types of nonmalignant chronic pain syndromes, including osteoarthritis. They concluded that opioid medications can be safely and effectively prescribed with relatively little risk of producing opioid abuse behavior.111 Many articles review the use of opioid regimens for treating geriatric chronic pain?, 5 5s52, 71,73, 78, The protocol for prescribing opioids for the elderly should be similar to that for all ages. The World Health Organization (WHO) analgesic ladder is followed. This protocol advocates using a tiered system whereby less potent drugs are used first until the patient is comfortable with minimal side effects. Remembering the physiology of aging, use of this system can decrease overall complication rates. First-tier drugs include non-opioids such as NSAIDs, acetaminophen, tricyclic antidepressants, and tramadol. Second-level medications include the "weak" opioids, such as combination drugs with acetaminophen and codeine, oxycodone, or hydrocodone. Third-tier medications include all the other opioids, both short- and long-acting. The guidelines to follow when devising a chronic pain analgesic regimen start with using a combination of medications to cut down on the side effects of any one of the drugs separately. When considering whch drug combinations to use, using drugs that work on the pain pathways at different points will give additive or synergistic results. If analgesia requires use of third-level medications from the WHO ladder, long-acting opioids frequently maintain analgesic blood levels within the therapeutic window more efficiently than the use of shortacting opioids. Prescribing the long-acting opioids on a set dose basis also helps to maintain more effective blood levels than giving medications on an as needed basis. PRN dosing only maintains the analgesic blood levels in the therapeutic window for approximately one third of the time. This means that two thirds of the time the patient is either being overdosed or underdosed and is in pain. Because of the unique physiology, pharmacodynamics, and pharmacokinetics of the elderly, the use of long-acting opioids can lead to an even longer duration of action and potential side effects. When elderly patients are unable to tolerate the use of long-acting opioids, several "tricks" may be tried. Try spreading out the dosing schedule to intervals that are longer than usual; for example, dosing medications that normally last for 6 to 8 hours, give every 12 hours. If the patient still doesn't tolerate the use of the long-acting opioids, the use of short-acting opioids on a set dose basis may give the same effect ( e g , giving codeine or oxycodone every 6 hours around the clock. The use of set dose non-opioids, such as tramadol, again possibly at an increased dosing interval (e.g., every 6-8 hours), can produce good analgesia with decreased side effects. Tramadol's mechanism of action appears to be mediated by both p, opioid receptor stimulation and irhbition of monoamine uptake.l13 Tramadol in a study comparing its use to acetaminophen with codeine was found to provide equivalent pain relief without serious NSAID or opioid adverse effects.l16 When conservative treatment fails, patients with intractable pain or functional incapacitation may need surgery. Orthopedic procedures frequently needed include debridement and removal of loose bodies, osteotomy, and partial and total joint replacements.

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Lower Back Pain Pain in general seems to be quite common among older people, occurring in 25% to 50% of community-dwelling people over the age of 60.45 In this population, a significant proportion of these painful conditions seem to involve the musculoskeletal system, including the lower back. In a study of the prevalence of pain in the general population, the back was among the most frequently identified anatomical regions for persistent pain.21It has been estimated that approximately 300,000 Americans over the age of 65 have activity limitations resulting from back or spine impairments.1ooIn the Iowa 65+ Rural Health Study, which studied a random group of noninstitutionalized persons over the age of 65, the incidence of low back pain was approximately 20% in the year prior to the survey.79Although this study showed a decrease in the prevalence of low back pain with advancing age, it still remained a significant health issue in the elderly, resulting in significant functional limitation and increased health care usage. In fact, 15% to 40% of elderly patients with low back pain reported significant impairment in the performance of basic physical activities. Treatment of low back pain in the elderly is important in preventing further functional limitation in these individuals who are so often afflicted with other comorbid conditions. Acute low back pain is often a self-limiting illness with an estimated 90% of affected individuals recovering in 3 months. However, in the elderly, where back pain can be the presenting symptom of more serious disease processes, a more careful evaluation is often indicated. For example, in one retrospective review of patients over the age of 50 years presenting for evaluation of low back or sciatic pain, the reported prevalence of malignancy was 7%.4l Other risk factors for malignancy include a previous history of cancer, unexplained weight loss, pain duration of greater than 1 month, and failure to improve with more conservative thera~y.2~ In light of these data, any elderly patient with back pain and known or suspected malignancy must be evaluated for the presence of metastatic disease, usually with a bone scan. In addition, the incidence of certain primary skeletal malignancies, such as multiple myeloma, increases substantially after age 40. Although uncommon, skeletal tuberculosis is more common in the elderly and should be included in the differential diagnosis of new onset back pain, particularly when associated with spinal tenderness and fever. A careful history and physical examination may help in distinguishing between back pain owing to serious systemic disease and that owing to more benign conditions such as spinal stenosis and facet joint disease.= For example, in the patient with an insidious onset of low back pain and a prominent component of nocturnal or rest pain, a more careful evaluation for the presence of metastatic disease is probably warranted. Although more serious spine pathology is more common in the elderly, this does not warrant the routine use of radiographic and laboratory evaluation in all patients who present with low back pain. In one large, retrospective study reviewing 68,000 conventional lumbar-sacral spine examinations, clinically unsuspected positive findings were found in only 1 of 2500.99 An exhaustive search for more treatable and often more serious spinal pathology is especially important in the elderly, but this evaluation must be guided by clinical judgment such that it may be completed in an organized and cost-effective manner. Once more serious spinal pathology has been excluded, the physician may focus attention on the more common causes of low back pain. Although back pain may result from injury to several spinal structures, it appears that most geriatric back pain is secondary to degenerative disease involving both the

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facet joints and intervertebral ~ynchondroses.~~~ By age 65, most people have radiographic evidence of degenerative spine disease and studies have shown that this process may begin as early as the third decade." More specifically, the aging process is associated with thinning of the intervertebral discs owing to a decrease in water content of the nucleus pulposus. However, numerous studies have confirmed the lack of correlation between radiographic or pathologic findings and patient complaints. Treatment should be based on the history and physical examination with radiographic evidence used to support the diagnosis. Lumbar spinal stenosis is a common diagnosis among the elderly, where degenerative disease of the spine may often lead to central canal narrowing. The canal narrowing may be secondary to osteophyte formation, disc bulging/ herniation, facet hypertrophy, or spondylolisthesis. Studies have shown that the mean age at the time of surgery for spinal stenosis is 55 years, with an average symptom duration of 4 years.137Spinal stenosis is associated with pain in the legs and occasionally neurologic deficits that occur after walking, which is not relieved by cessation of walking (neurogenic claudication). Pain may also occur with prolonged standing (in contrast to vascular claudication) and is usually relieved by lying down or flexion at the waist (a sitting position). No physical findings appear to be specific for spinal stenosis and the diagnosis is often made based on the history alone. If needed, CT or MR imaging can be used to confirm the diagnosis. Barring progressive neurologic impairment, conservative therapy with analgesics, NSAIDs, and bedrest is the mainstay of treatment. The use of other modalities to treat spinal stenosis, such as epidural steroid injections, is still widely debated. Although epidural steroids cannot relieve the pressure of the spinal structure^,^^ studies have documented initial success rates as high as 81% to 90% in relieving pain secondary to spinal ~ten0sis.l~~ However, sustained pain relief at 6 months was only 0% to 1.5% compared with 3.7% to 10% in patients with a herniated disc and nerve root irritation.'O It may be in those cases where spinal stenosis is associated with acute nerve root irritation that epidural steroids are most beneficial? The short duration of relief may be owing to the magnitude of the bony compression resulting in nerve root inflammation and, eventually, nerve root fibrosis. Epidural steroids may be efficacious in those patients with spinal stenosis and a superimposed acute radicular syndrome, but its use in chronic stable low back pain is less well documented. Although the peak prevalence of herniated lumbar discs is between the ages of 30 and 55 years,128it also occurs frequently in the elderly population. However, anatomic evidence of a herniated disc is found in approximately 20% to 30% of clinically asymptomatic individuals, indicating that disc herniation is not always associated with significant nerve root irritation. As mentioned previously, aging is associated with degeneration of the intervertebral discs which often results in marked narrowing of the disc space. This phenomenon can be associated with osteophyte formation, osteoarthritis of the facet joints, and disc bulging or herniation. The pain associated with disc bulginglhemiation is either secondary to distension of the posterior longitudinal ligament or to direct compression of adjacent nerve roots. However, recent evidence supports the contention that extruded nucleus pulposus may initiate an inflammatory response in the absence of direct nerve root compression. High levels of phospholipase A2 contained within the liberated nucleus pulposus may initiate the inflammatory response.124 The presence of this inflammatory reaction is the premise for using epidurally administered steroids in the treatment of acute radicular back pain secondary to a herniated nucleus pulposus. However, acute low back pain secondary

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to a herniated disc often resolves on its own, so intitution of therapy must be based on the degree of functional impairment. One advantage of epidural steroids is that, in patients who respond, approximately 96% improve within 6 days,56which is often substantially faster than with bedrest alone.18In a population where functional autonomy is of primary importance, treatments that speed recovery are especially beneficial. The success rate for epidurally administered . ~ general, steroids ranges from 25% to 75% in several well-controlled ~ t u d i e sIn patients with acute-onset radicular pain tend to respond better to epidural steroids than those with chronic stable back pain. In fact, patients with back pain for less than 6 months had an improvement rate of 69% compared with 48% for patients with symptoms lasting more than 6 months.' One study showed a significant reduction in analgesic requirements at 3 months' follow-up when epidural steroids were used to treat patients with back pain and documented degenerative disc The latter may be especially important in the elderly who are often prone to unwanted medication side effects. In 63% of patients, epidural steroid injections provided sustained relief for at least 6 months.141 However, even temporary relief of pain may allow for physical therapy and training in proper body mechanics, which may be important in maintaining joint range of motion and flexibility. A large number of studies have been published confirming the safety of epidural steroid injections.* Epidural steroid injections should be used with caution in diabetic patients, who may be at added risk for epidural infections and whose glucose control may be compromised. The fluid retention that may result from repeated epidural steroid injections may be deleterious in the patient with marginal cardiac reserve. Because cardiac disease and diabetes are more frequent in the elderly, one must weigh the potential benefits against the potential risks. Several published studies have documented the suppression of the pituitary-adrenal axis by epidurally administered steroids.35,72 However, suppression may be avoided by using a low dose of injected steroid (40-80 mg of methylprednisolone acetate) and by allowing approximately 2 to 3 weeks between injections.35, 72 Although infrequent complications do occur, it appears that the overall safety and efficacy of epidural steroids is well documented in carefully selected elders with low back pain. In addition to discogenic causes for low back pain, facet disease may play a significant role in the elderly who often suffer from multi-joint arthritic disease. The underlying pathology seems to be degenerative joint disease within the facet joints, although these radiographic findings may be present without producing pain.81The presentation of facet joint disease is often nonspecific, and one must often rely on clinical suspicion and response to therapeutic maneuvers for a more definitive diagnosis. Numerous studies have been published on the use of intraarticular steroid and local anesthetic injections in both the diagnosis and treatment of facet-joint disease.81,83 Initial therapeutic success rates as high as 75% have been reported,81although the long-term benefit is less well documented. Systemic absorption of deposited steroids resulting in suppression of the hypothalamic-pituitary-adrenal axis, although infrequent, is possible following intrafacet injecti0ns.3~As mentioned for epidural steroids, facet joint injections should be done with caution in elderly individuals with diabetes or marginal cardiac reserve. In those patients who respond to intraarticular steroids and/or local anesthetics, more sustained benefit may be achieved with radiofrequency neurolysis of the involved medial branch of the posterior spinal nerve ram~s.'"~ However, even the results of neurolysis are often temporary and repeat procedures may be necessary. Although not as responsive to therapeutic interventions, certain pain syn-

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dromes may occur with an increased frequency in the elderly. Specifically, the elderly may be more prone to osteoporosis and resultant vertebral compression fractures,22Paget’s disease of the spine, and, rarely, late complications of ankylosing spondylitis. Initially, these patients are managed medically, with consideration of surgery only in those patients with significant functional limitations. In such cases, the pain specialist’s role is often limited to the management of an appropriate oral analgesic regimen. However, therapeutic interventions, such as epidural steroid injections or intrafacet steroid injections, may be appropriate for a select group of elderly individuals with specific pain syndromes.

Neuropathy Neuropathy is defined as a disturbance in nerve function or structure. Whatever the cause, the anatomic pathophysiology is owing to axonal degeneration and segmental demyelination. This leads to selective loss of large fibers (e.g., A[p]) that have an inhibitory affect on pain transmission from the periphery according to the Gate Control Theory, with preferential regeneration of smaller fibers (e.g., A[6] and C) that have stimulatory input regarding pain sensation. The sum total of these changes is increased pain sensation from the periphery. Other peripheral mechanisms for neuropathic pain include neuroma formation leading to abnormal spontaneous uncoordinated neuronal firing and a contribution of sympathetic mediation to the pain. Changes at the levels of the dorsal root ganglia, the dorsal horn neurons, and the brain itself have also been associated with neuropathic pain?8 The origins of neuropathies are vast. The most common cause is diabetes m e l l i t u ~In . ~ a~ study of 4400 patients with diabetes, 45% developed neuropathy during the course of their disease.1osPain occurs in approximately 75% of cases of neuropathy. The symptoms associated with neuropathic pain are paroxysmal, sharp, lancinating, shock-like pain. The pain follows a dermatomal distribution and may have concomitant hyperesthesia or allodynia. Pain can also occur in areas of sensory deficit known as anesthesia dolorosa. Diabetic neuropathy can be dealt with in two different ways, prevention and treatment. The Diabetes Control and Complications Trial demonstrated that intensive diabetes treatment (three or more insulin injections daily or an external subcutaneous insulin pump and frequent blood glucose monitoring) effectively delays the onset and slows the progression of long-term microvascular and neurologic cornpli~ations.~~ It was shown that electrophysiologic abnormalities associated with diabetic neuropathy can be delayed or prevented by intensive diabetes treatment,3O and that the risk for clinical neuropathy could be reduced by up to 64%.3l Many articles review the different treatment options for diabetic neuropathy.lz,40 Tricyclic antidepressants (TCAs) are among the first-line analgesics used against neuropathic pain. Their mechanism of action involves the inhibition of the reuptake of serotonin and norepinephrine in the descending inhibitory tracts of the spinal cord. Amitriptyline has been the most studied TCA analgesic for neuropathic pain. Specifically, amitriptyline has been shown to relieve the pain of diabetic neuropathy independent of mood elevati0n.8~ Amitriptyline though, especially in a side effect-prone group like the elderly, can cause many complications such as sedation, urinary retention, and orthostatic hypotension. Desipramine has the least anticholinergic side effects of the firstgeneration tricyclic antidepressants and causes relatively little sedation. It too has been demonstrated to be analgesic in diabetic neuropathy.88In a comparison

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study, desipramine was found to relieve pain caused by diabetic neuropathy with efficacy similar to that of amitriptyline and with less overall side effectss6 In the geriatric population with neuropathic pain, desipramine might be a better choice than amitriptyline when a TCA is indicated. Anticonvulsants have been used to treat neuropathic pain for many years. Both phenytoin and carbamazepine have been shown to be effective neuropathic pain medications but with each causing an extensive list of side e f f e ~ t s . ~ ~ , ' ~ ~ Newer formulations of anticonvulsants have recently been developed that also treat the pain of diabetic neuropathy but with significantly less side effects. Gabapentin is an example of one of these new anticonvulsants that has recently been shown to be effective for the symptomatic treatment of painful neuropathy,118,119 including patients with diabetic neuropathy? The only statistically significant side effects were dizziness and somnolence. Gabapentin might, therefore, be considered the anticonvulsant of choice for neuropathic pain in the elderly. Other classes of drugs also have been used to treat neuropathic pain. Mexiletine, an analogue of lidocaine, can be given orally and has demonstrated an analgesic effect on chronic painful diabetic neuropathy.26It seems to work best against burning or stabbing types of pain, and side effects are few. Capsaicin, a topical analgesic derived from chili peppers, was studied by the Capsaicin Study Group.13 Diabetic patients with peripheral painful polyneuropathy or radiculopathy showed decreased pain but had localized adverse effects such as burning and rash. Still, systemic side effects are minimal and, in the geriatric population, this should be considered as an alternative analgesic. Postherpetic Neuralgia

The incidence of acute herpes zoster and postherpetic neuralgia (PHN) increases with age.62Although acute herpes infection can be temporarily disabling, it is PHN that is important in terms of chronic morbidity. PHN, which is generally defined as pain persisting for more than a month after the disappearance of the rash of acute herpes zoster, occurs in the general population at a rate of approximately 9.3% to 14.3%.67, 114 It may occur in up to 75% of those over the age of 70.67PHN generally resolves within 3 months in about 50% of affected individuals and only persists beyond 5 years in about 2% of cases.67,114 Unfortunately, a lot of the long-standing cases are in the geriatric age group and often result in a chronic debilitating illness. The pain of PHN is generally described as a constant burning discomfort on which may be superimposed intermittent lancinating pains and dysesthesias.l17PHN is also frequently associated with allodynia and hyperpathia in the affected dermatome. It is unclear whether the pain is primarily of central or peripheral origin. One popular theory is that the preferential destruction of large (inhibitory) myelinated fibers, accompanied by a more rapid regeneration of small (nociceptive)fibers results in an overall predominance of excitatory influences on wide dynamic range neurons in the spinal cord.117It is possible that the aging process may be associated with a preferential loss of large myelinated nerve fiber function,lMwhich may, in part, account for the increased incidence and severity of PHN in the elderly. The refractoriness of PHN to most conventional treatments makes adequate analgesia a daunting task, especially in the frail elderly patient. Because longer duration PHN carries with it a poorer prognosis, it is important to institute therapy early. Although studies have shown that both intravenous and hgh-

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dose oral acyclovir is effective in accelerating the cutaneous healing in acute herpes zoster, studies have not confirmed its use in the prevention of PHN.68,90 However, it has been shown that patients treated with acyclovir during the acute zoster phase obtain relief with subsequent antidepressant therapy in half the time required by those who did not receive acyclovir? Acyclovir seems to be most effective in the treatment of acute herpes zoster when it is started within 48 hours of the onset of the rash. In contrast, the drug famciclovir, when used to treat acute herpes zoster, accelerates the rate of lesion resolution and more importantly is associated with a significant reduction in the duration of pHN.138The role of corticosteroids in the prevention of PHN is also controversial. A placebo-controlled study by Esmann et a13*in 1987 showed no reduction in the incidence of PHN at 6 months when prednisolone was added to oral acyclovir. When prednisolone is used, it is generally recommended at a dosage of 60 mg/d, with a gradual dose reduction over 2 weeks. A small number of studies have documented the efficacy of local anesthetic injections and sympathetic nerve blocks17,132 in controlling the pain of acute herpes zoster, enhancing the healing of acute lesions, and in preventing the subsequent development of PHN. In treating acute and postherpetic neuralgia, the sympathetic chain has been blocked at all levels including the stellate, thoracic, and lumbar paravertebra1 ganglia. A recent study showed that high thoracic epidural block (Tl-T4) was as effective in controlling the pain associated with trigeminal and cervical acute herpes zoster as a stellate ganglion block at the C6 level.& It has been postulated that PHN is associated with sympathetically mediated selective large nerve fiber ischemia which is prevented or reversed with sympathetic blockade. This hypothesis may explain why sympathetic nerve blocks are less effective once PHN is well established, because irreversible ischemic nerve damage may have already occurred. Although local anesthetic blockade of sympathetic ganglia is the most widely accepted techmque, the use of opioids such as fentanyl, along with local anesthetics to augment the autonomic blockade also has been described in the literature.49Studies that have confirmed the use of sympathetic blocks in the prevention of PHN132have emphasized the early institution of such therapy, usually within 6 to 8 weeks of the acute eruption. The pain associated with well-established PHN can be controlled both with medications and more invasive modalities. The latter may be especially important in the elderly in whom medication side effects may be more pronounced. Currently accepted first-line drugs for PHN include both TCAs and anticonvulsants. Amitriptyline, a combined serotonin and norepinephrine reuptake blocker, has proven efficacy in the treatment of PHN.89Studies have shown that old age is associated with a prolonged elimination half-life of amitriptyline as well as an increase in steady-state concentrations.'01,125 Side effects may be more pronounced. Anticholinergic side effects such as dry mouth, blurred vision, tachycardia, urinary retention, constipation, orthostatic hypotension, confusion, delirium, and cognitive impairment may be especially distressing for the elderly individual. It is, therefore, recommended that amitriptyline be started at an initial dosage of 10 to 25 mg 2 hours before bedtime, and that the dosage be adjusted in weekly increments of 10 to 25 mg until the desired effect is acheved. An adequate therapeutic trial may be up to 4 to 6 weeks.l12Studies have shown that if patients are given low-dose amitriptyline within 3 to 6 months of acute infection, their chances of achieving significant pain reduction is appreciably increa~ed.~ Although selective serotonin reuptake blockers may be associated with fewer anticholinergic side effects, studies have not documented their efficacy in PHN. Desipramine, a selective norepinephrine reuptake blocker, may be of some use in the elderly patient in whom amitriptyline may be excessively

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sedating. Anticonvulsants, particularly ~arbamazepine'~~ and more recently gabapentin and lamotrigine, have also been widely used in the treatment of PHN. A recent study showed that even when dosages of gabapentin as high as 3600 mg/d were used in a population with an average age of 73 years, there were no reports of serious drug-related side effects.lZ0These drugs act by suppressing spontaneous neuronal firing through membrane-stabilizing and seem to be most effective in managing pain states with a prominent lancinating component. Carbamazepine can be used in doses between 400 to 800 mg/d, but some patients may respond to as little as 200 mg/d. The concurrent use of which carbamazepine and TCAs may result in elevated blood levels of necessitates careful monitoring of carbamazepine levels such that toxic levels are not achieved. Significant side effects may occur with anticonvulsant therapy including nausea, vomiting, ataxia, lethargy, confusion, and rarely agranulocytosis. These side effects may be particularly detrimental in the elderly where they may significantly interfere with the patients' activities of daily living. Although less well studied, agents such as baclofen, topical clonidine patch, and prazosin may be efficacious in situations where a significant proportion of the pain is sympathetically maintained.76 Analgesic medications such as NSAIDs and opioids are notoriously ineffective in the treatment of PHN. Nonsteroidal anti-inflammatory drugs may be particularly effective in those patients in whom PHN is associated with a significant peripheral inflammatory component. In light of the serious side effects of NSAIDs, frequent monitoring of renal function and hematocrit would be of particular importance in the elderly patient. Recently, the use of a topical aspirin/ diethyl ether mixture has been proven efficacious in the treatment of pain associated with both acute and postherpetic ne~ralgia.2~ The topical treatment was most effective in patients with trigeminal involvement, less severe pain, and pain with a dysesthetic quality to it. More importantly, the use of topical anti-inflammatory agents may not be associated with significant gastrointestinal and renal side effects, and would be more appropriate for use in the elderly. The clearance of opioid analgesics, such as morphine, is decreased in individuals over the age of 50 and this can result in cumulative drug effects.51,140 The decreased clearance results in not only a greater analgesic response, but also an increase in unwanted side effects including nausea, vomiting, pruritis, respiratory depression, and constipation. It is apparent from the aforementioned data that the potential benefits of using NSAIDs and opioids in the treatment of PHN must be carefully weighed against the risks of using these medications in the very frail and elderly. The treatment of PHN pain with topical 0.025% capsaicin may be of particular use in the debilitated elderly. Prolonged application of capsaicin over the affected area results in depletion of substance P from sensory nerve endings, resulting in a diminution of pain.115Treatment may be effective in as many as 75% of patients with chronic postherpetic ~ a i n . 6Capsaicin ~ should be applied 4 to 5 times daily, and an adequate therapeutic trial should persist for at least 4 weeks.142Recent studies have determined its use in pain associated with herpes zoster ophthalmicus neuralgia, when applied to the affected dermatome 5 times daily over a 4-week period.= Significant side effects include burning and hyperesthesia at the site of administration, which may result in discontinuation of the drug in about one third of cases. The burning may become more bearable after the first week of treatment and can be effectively controlled by pretreating the involved skin with 5% lidocaine ointment. In light of its relative safety and

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efficacy, it seems reasonable to consider topical capsaicin as a first-line treatment for PHN in the elderly patient. Although the N-methyl-D-aspartate receptor antagonists ketamine and dextromethorphan have been reported to have efficacy in the treatment of PHN, often intolerable side effects probably preclude their use in the elderly. Recently, the use of a subcutaneous infusion of ketamine resulted in a reduction in both spontaneous and evoked pain, but was associated with itching and induration at the infusion site, as well as nausea, fatigue, and dizziness.36It does not appear that these agents should be used to treat PHN in elderly individuals where these side effects may not be tolerated. Because treatment of PHN with medications is often associated with unwanted side effects, it appears incumbent upon the practitioner to make every effort to use other treatment modalities so that the overall medication dosage and frequency may be reduced. Currently accepted modalities include local infiltration of the area of pain with local anesthetics and steroids, the use of TENS, sympathetic nerve blocks, epidural injection of local anesthetics and steroids, and possibly the use of more invasive modalities such as dorsal column stimulation or intrathecal infusion of opioid agonists. Although controlled studies are lacking, anecdotal evidence exists to substantiate the efficacy of epidurally administered steroids and local anesthetics in the treatment of PHN. A study by Forrest in which patients were treated with a series of three epidural steroid injections at weekly intervals resulted in an 89% success rate at 1-year followup.53 The administration of subanalgesic doses of the combination of ketamine, morphine, and bupivacaine in the thoracic epidural space resulted in a substantial reduction of allodynic pain in one Although local anesthetic infiltration of the involved dermatome may provide symptomatic relief, no studies confirming any sustained benefit are currently available. The topical application of lidocaine patches was effective in controlling pain in one study.lZ1No systemic side effects were noted when these patches were applied over a 12-hour period, indicating that use in the elderly may be both safe and effective. Intravenous lidocaine also has been used successfully in the treatment of postherpetic neuralbut in the elderly patient who may also have concurrent cardiac disease, the risks may outweigh any potential benefit. Recently, one study has described the use of 5% lidocaine with 7.5% dextrose in a patient with occipital postherpetic neuralgia to produce occipital nerve block and provide prolonged analgesia.16 The study patient had sustained reduction in his pain scores for approximately 8 months. Transcutaneous electrical nerve stimulation has proven to be effective in the treatment of PHN, but the relief is often temporary with benefits often waning over a 6-month period.‘= TENS may be a very useful adjuvant in the frail elderly patient, especially when combined with carefully titrated medications and physical and behavioral therapy. More recently, implantable dorsal column stimulators and intrathecal infusion devices have been used to treat chronic intractable nonmalignant pain.76,Io2 The use of these modalities in the treatment of PHN has not been adequately studied to date to suggest their routine use in this condition. However, it does appear that these modalities would be particularly beneficial in the elderly patient who is unable to tolerate high-dose systemic medications. CONCLUSION

Geriatric patients are not just ”old adults.” They have a unique physiology that has immense implications for the treatment of their chronic pain syndromes.

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A n intimate knowledge of the pharmacokinetics a n d pharmacodynamics of the analgesics used for geriatric p a i n is essential to increase p a i n relief a n d minimize side effects. The ability to perform nerve blocks and other nonpharmacologic analgesic modalities can further maximize pain management efficiency. The anesthesiologist stands as a n ideal consultant for the treatment of geriatric pain.

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