Objectives: Upon completion of this course the student will have a fundamental knowledge of pharmacologic, physical, and psychosocial ways to manage cancer pain. The approaches provided are both practical and flexible for management of cancer pain in adults
Note: Because pain problems in patients with HIV/AIDS are often assessed and treated using the same approaches as those used for cancer pain, HIV/AIDS pain is described as well.
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Cancer pain can be managed effectively through relatively simple means in up to 90 percent of the 8 million Americans who have cancer or a history of cancer.
Unfortunately, pain associated with cancer is frequently under-treated.
Although cancer pain or associated symptoms cannot always be entirely eliminated, appropriate use of available therapies can effectively relieve pain in the great majority of patients. Pain management improves the patient's quality of life throughout all stages of the disease.
State and local laws often restrict the medical use of opioids to relieve cancer pain, and third-party payers may not reimburse for noninvasive pain control treatments.
Thus, clinicians should work with regulators, State cancer pain initiatives, or other groups to eliminate these health care system barriers to effective pain management.
Table 1 lists these and other barriers to effective pain management. Changes in health care delivery may create additional disincentives for clinicians to practice effective pain management.
Table 1. Barriers to Cancer Pain Management
Problems related to health care professionals:


Inadequate knowledge of pain management


Poor assessment of pain
 Concern about regulation of controlled substances
Fear of patient addiction
Concern about side effects of analgesics
 Concern about patients becoming tolerant to analgesics
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Problems related to patients:
Reluctance to report pain.
 Concern about distracting physicians from treatment of underlying disease
 Fear that pain means disease is worse
 Concern about not being a "good" patient
Reluctance to take pain medications.
 Fear of addiction or of being thought of as an addict
 Worries about unmanageable side effects
 Concern about becoming tolerant to pain medications
Problems related to the health care system


Low priority given to cancer pain treatment
 Inadequate reimbursement
The most appropriate treatment may not be reimbursed or may be too costly for patients and families
 Restrictive regulation of controlled substances
 Problems of availability of treatment or access to it
Flexibility is the key to managing cancer pain. As patients vary in diagnosis, stage of disease, responses to pain and interventions, and personal preferences, so must pain management. Figure 1 emphasizes that the recommended clinical approach focuses on patient involvement.
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Figure 1. Recommended Clinical Approach
A. Ask about pain regularly. Assess pain systematically.
B. Believe the patient and family in their reports of pain and what relieves it.
C. Choose pain control options appropriate for the patient, family, and setting.
D. Deliver interventions in a timely, logical, coordinated fashion.
E. Empower patients and their families. Enable patients to control their course to the greatest extent possible.
Effective pain management is best achieved by a team approach involving patients, their families, and health care providers. The clinician should:
 Discuss pain and its management with patients and their families.
 Encourage patients to be active participants in their care.
 Reassure patients who are reluctant to report pain that there are many safe and effective ways to relieve pain.
 Consider the cost of proposed drugs and technologies.
 Share documented pain assessment and management with other clinicians
Florida Heart CPR* Pain Mgt in Cancer Patients

treating the patient.
 Know state/local regulations for controlled substances.
Failure to assess pain is a critical factor leading to undertreatment. Assessment involves both the clinician and the patient. It should occur:
 At regular intervals after initiation of treatment
 At each new report of pain
 At a suitable interval after pharmacologic or nonpharmacologic intervention, e.g., 15-30 minutes after parenteral drug therapy and 1 hour after oral administration
Identifying the etiology of pain is essential to its management. Clinicians treating patients with cancer should recognize the common cancer pain syndromes (Table
2). Prompt diagnosis and treatment of these syndromes can reduce morbidity associated with unrelieved pain.
The goal of the initial assessment of pain is to characterize the pathophysiology of the pain and to determine the intensity of the pain and its impact on the patient's ability to function. Essential to initial assessment are:
 Detailed history
 Physical examination
 Psychosocial assessment
 Diagnostic evaluation
The mainstay of pain assessment is the patient self-report. To enhance pain management across all settings, clinicians should teach families to use pain assessment tools in their homes. The clinician should help the patient to describe:




Pain. Listen to the patient's descriptive words about the quality of the pain; these provide valuable clues to its etiology. Elicit the temporal features including onset, duration, and diurnal variation.
Location. Ask the patient to indicate the exact location of the pain on his or her body, or on a body diagram and whether it radiates.
Intensity or Severity. Encourage the patient to keep a log of pain intensity scores to report during follow-up visits or by telephone. Examples of simple self-report pain intensity scales include simple, descriptive, numeric, and visual analogue scales.
Aggravating and Relieving Factors. Ask the patient to identify factors which
3
Florida Heart CPR* Pain Mgt in Cancer Patients

cause the most pain and also what relieves the pain.
 Cognitive Response to Pain. Note behavior suggesting pain in patients who are cognitively impaired or who have communication problems relating to
 education, language, ethnicity, or culture. Use appropriate (e.g., simpler or translated) pain assessment tools.
Goals for Pain Control. Document the patient's preferred pain assessment tool and the goals for pain control (such as scores on a pain scale).
A thorough physical examination is required to determine the pathophysiology of pain. Specific features of the neurologic examination such as altered sensation
(hypoesthesia, hyperesthesia, hyperpathia, allodynia) in a painful area are suggestive of neuropathic pain. Physical findings of tumor growth and metastasis are also important to identify.
Continual assessment of cancer pain is crucial. Changes in pain pattern or the development of new pain should trigger diagnostic evaluation and modification of the treatment plan. Persistent pain indicates the need to consider other etiologies (e.g. related to disease progression or treatment) and alternative (perhaps more invasive) treatments.
Assessment of the Outcomes of Pain Management
Pain-related outcomes: Clinicians should document and be aware of outcomes of pain therapy. It is helpful to think of pain-related outcomes as primarily measured in two ways: decreased pain intensity and improvement in psychosocial functioning.
Using rating scales of pain intensity at its worst and on average, and also using pain interference scales can help clinicians monitor outcomes. Measurement of the percentage of pain relief is also useful, though measuring patient satisfaction is less useful because of the low expectations patients sometimes hold for pain control.
Drug-taking outcomes: Clinicians prescribing chronic opioids should also monitor and document patients' drug-taking behaviors. Outcomes related to addiction in cancer patients are rare but nonetheless should be periodically assessed; these assessments can be reassuring to patients. Tolerance and dependence are not addiction-related. Documentation of patients' compliance with regard to changes in dosing and duration of prescriptions is essential in all pain practice.
4
Drug therapy is the cornerstone of cancer pain management. It is effective, relatively low risk, inexpensive, and usually works quickly.
An essential principle in using medications to manage cancer pain is to individualize
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the regimen to the patient.
Even within the same family of analgesic drugs, individual variations in effects and side effects are well recognized. Principles of pharmacologic therapy begin with the
World Health Organization (WHO) ladder, a three-step hierarchy for analgesic pain management. WHO recommendations are based on worldwide availability of drugs, and not strictly on pharmacology. Substitution of drugs within a category should be tried before switching therapy:
 Use the simplest dosage schedules and least invasive pain management modalities first.
 For mild to moderate pain, use (unless contraindicated) aspirin, acetaminophen, or non-steroidal anti-inflammatory drug (NSAID; WHO ladder, Step 1).
 When pain persists or increases, add an opioid (WHO ladder, Step 2).
 If pain increases, increase the opioid potency or dose (WHO ladder, Step 3).
 Schedule doses regularly (i.e., "by the clock") to maintain the level of drug that will help prevent recurrence of pain. Ask for patient and family cooperation in establishing the effective level.
 Administer additional doses "as needed" for breakthrough pain.
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NSAIDs are effective for relief of mild pain, and may have an opioid dose-sparing effect that helps reduce side effects when given with opioids for moderate to severe pain. Acetaminophen is included with aspirin and other NSAIDs because it has similar analgesic potency although it lacks peripheral anti-inflammatory activity. Side effects can occur at any time, and patients who take acetaminophen or NSAIDs -- especially elderly patients -- should be followed carefully.
Dosage. Use patient response to determine the effective dosing interval for aspirin, acetaminophen, and other NSAIDs listed in Table 3. When pain relief is not attained with the maximum dosage of one NSAID, try other drugs within this category before abandoning NSAID therapy.
Route of Administration. Use readily available oral tablets, capsules, or liquid. During intervals of nausea and vomiting, use suppositories. Ketorolac tromethamine is the only NSAID available for parenteral use.
Contraindications. Patients taking NSAIDs (except acetaminophen) are at risk for platelet dysfunction that may impair blood clotting. Table 3 lists NSAIDs with minimal anti-platelet activity.
Other Side Effects. Follow patients carefully for adverse effects, which range from mild gastrointestinal discomfort to more serious problems, including:
Florida Heart CPR* Pain Mgt in Cancer Patients

 Renal failure
 Hepatic dysfunction
 Gastric ulceration
Because both NSAIDs and other drugs (e.g., warfarin, methotrexate, digoxin, cyclosporine, oral antidiabetic agents, and sulfonamide-containing drugs) are highly protein bound, there is potential for altered efficacy or toxicity when given simultaneously.
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Opioids
Opioids, the major class of analgesics used in management of moderate to severe pain, are effective, easily titrated, and have a favorable benefit-to-risk ratio.
Opioid tolerance and physical dependence do not equate with "addiction."
The predictable consequences of long-term opioid administration -- tolerance and physical dependence -- are often confused with psychological dependence
(addiction), that manifests as drug abuse. This misunderstanding can lead to ineffective prescribing, administering, or dispensing of opioids for cancer pain. The result is undertreatment.
Clinicians may be reluctant to give high doses of opioids to patients with advanced disease because of a fear of respiratory depression. Many patients with cancer pain become opioid tolerant during long-term opioid therapy. Therefore, the clinician's fear of shortening life by increasing opioid doses is usually unfounded. The clinician's ethical duty to benefit the patient by relieving pain supports increasing doses, even at the risk of side effects.
Opioids are classified as full morphine-like agonists, partial agonists, or mixed agonist-antagonists, depending on the specific receptors to which they bind and their activity at these receptors. The benefits of using opioids and the risks associated with their use vary among individuals. The following information about opioids is a brief discussion.
Full Agonists, including morphine, hydromorphone, codeine, oxycodone, hydrocodone, methadone, levorphanol, and fentanyl, are classified as such because their effectiveness with increasing doses is not limited by a "ceiling." Full agonists will not reverse or antagonize the effects of other full agonists given simultaneously.
 Morphine. The most commonly used opioid, morphine, is readily available in several forms, including sustained-release (8-24 hours duration of effectiveness) formulations for oral administration.
 Other Agonists. For the patient who experiences dose-limiting side effects with one oral opioid (e.g., hallucinations, nightmares, dysphoria, nausea, or mental clouding), other oral opioids should be tried before abandoning one
Florida Heart CPR* Pain Mgt in Cancer Patients

route in favor of another.
 Methadone. Given the reported clinical experience, methadone can be considered a very useful second- or third-line opioid for cancer pain management. However, given the high potency and unpredictable nature of response to this medication, inexperienced clinicians should be cautious. It is recommended that appropriate reference material is reviewed, or the support of an experienced colleague is requested when starting a patient on methadone for the first time.
There has been a revival in interest in using methadone for the management of pain in cancer patients. Publications have been in the form of case reports, 1-7 outcome surveys, 8-12 and reviews.
13,14 Subcutaneous methadone has been reported to cause tissue irritation at the injection site. Success has been reported using methadone orally, intravenously, and by suppository.
7
Methadone is a synthetic opioid agonist that has been reported to have a number of unique characteristics. These include excellent oral and rectal absorption, no known active metabolites, prolonged duration of action resulting in longer administration intervals, and lower cost than other opioids. The published clinical experience has highlighted these important considerations:
Methadone used for chronic pain management demonstrates a much higher potency than the 1:1 or 1:2 methadone to morphine ratio that is generally reported in tables of opioid equivalence. Clinical results have reported methadone as ten times more potent than morphine.
Patients on high opioid doses exhibiting both inadequate pain control and significant opioid-related toxicity have achieved good pain control with rotation to methadone.
The idiosyncratic individual response to methadone (because of issues of potency, accumulation, and drug elimination) has resulted in the recommendation that this medication should be used with extreme caution.
A careful method of rotation to methadone over a 1 week period has been proposed.
8,10
On day 1, the total 24 hour opioid dose is decreased by 30%. This is replaced by a dose of methadone calculated at a ratio of ten to one compared to a morphineequivalent dose (methadone given at 1/10 the morphine-equivalent dose), given on a regular, eight-hourly schedule. Patients are followed closely, with in-patient monitoring preferred.
On day 2 the original opioid is decreased by a further 30%, and the methadone dose increased by 10%-30%, based on clinical assessments of patient's analgesic requirements. A patient not tolerating the conversion should consult with a pain management expert. If one has concerns regarding drowsiness or respiratory
Florida Heart CPR* Pain Mgt in Cancer Patients

depression, the methadone dose should not be increased and the original opioid dose may be decreased by a further 30%. If at all uncertain, hold administration of methadone and consult an experienced colleague.
On day 3, if the patient is not sedated (in mental acuity) and respiration is not compromised, the original opioid is discontinued and the methadone dose increased by 0%-30% as determined by the clinical assessment. At this point, the rescue dose of opioid is also switched to methadone, calculated at 10% of the 24-hour dose.
Daily assessment should be continued on days 4-7, watching for sedation, respiratory depression, and analgesic efficacy. Despite using this cautious approach, respiratory depression has been observed, requiring intervention with subcutaneous naloxone.
2
In some countries there are restrictions that do not apply to other opioids on the ability of physicians to prescribe methadone. In the U.S. this pertains to methadone for maintenance of addiction. Methadone is not restricted when used for pain management. However, physicians should carefully document the use of methadone for pain management.
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Partial Agonists, such as buprenorphine, have less effect than full agonists at opioid receptors. They are subject to a ceiling effect, thus are less effective analgesics.
Mixed Agonist-Antagonists block or are neutral at one type of opioid receptor while activating a different opioid receptor. Mixed agonist-antagonists are contraindicated for use in the patient receiving an opioid agonist because they may precipitate a withdrawal syndrome and increase pain. Mixed agonist-antagonists include pentazocine (Talwin), butorphanol tartrate (Stadol), denocine (Dalgan), and nalbuphine hydrochloride (Nubain). Their analgesic effectiveness is limited by a dose-related ceiling effect.
Dosage
The appropriate dose is the amount of opioid that controls pain with the fewest side effects. The need for increased doses of opioid often reflects progression of the disease and not analgesic tolerance. If analgesic tolerance occurs, it can be overcome by increasing the dose or changing the agent to another opioid agonist.
Tables 4 and 5 list equianalgesic initial doses of commonly used opioids for adults weighing over and under 50 kg (110 pounds), respectively. Points to keep in mind include:


Titration. Increase or decrease the next dose by one-quarter to one-half of the previous dose. Rapid dose escalation should be accompanied by close monitoring for efficacy and side effects.
Route conversion. When changing from the oral to the rectal route, begin with the same dosage as had been given orally, then titrate upward frequently and carefully. Lower doses are required for parenteral routes but are similar for
Florida Heart CPR* Pain Mgt in Cancer Patients

subcutaneous, intramuscular, and intravenous routes.
 Schedule. Prevent recurring pain rather than having to subdue it. Give analgesics on a regular schedule to prevent a loss of effectiveness between doses.
 Tolerance. Assume that patients actively abusing heroin or prescription opioids (including methadone) have some pharmacologic tolerance that will require higher starting doses and shorter dosing intervals.
 Cessation of opioids. When a patient becomes pain free as a result of cancer treatment or palliation (e.g., nerve destruction), gradually decrease the opioid

 to avoid the withdrawal.
Opioid therapy in Special populations. Special considerations should be given for opioid use in elderly, children, persons physically or cognitively impaired, and known or suspected drug abusers.
Opiod rotation. A series of case reports have demonstrated the clinical problem of inadequate pain control with escalating opioid doses in the presence of dose-limiting toxic effects including hallucinations, confusion, hyperalgesia, myoclonus, sedation, and nausea.
4,10,16-18 It was suggested that these problems could be managed by switching to an alternative opioid with the result being improved pain management and decreasing toxic effects. The improvement with opioid rotation, although predominately demonstrated initially with morphine, has also been reported with other opioids.
19-21 A series of outcome surveys has demonstrated that the toxic effects of opioid can be relieved by opioid rotation with substitution of a different opioid in an equianalgesic dose.
9,22-24 The major area of concern has been with the conversion to methadone. Methadone has been demonstrated to be much more potent than previously described. It has been reported that the equianalgesic dose can be five to ten times higher than the previously quoted oral methadone to morphine ratio of 1:1.
It has been suggested that rather than opioid rotation, a less complicated approach would be to reassess the clinical situation and use of adjuvant analgesics, decrease the opioid dose if possible, use medical management for the opioid-related sideeffects, and correct any contributing metabolic abnormalities.
25,26 Nevertheless, there does appear to be an emerging consensus that opioid rotation does have a useful role when pain control remains inadequate with escalating opioid doses, and the opioid results in unacceptable opioid-related side-effects.
25-27
9
Morphine, as the strong opioid metabolite of choice for the management of cancer pain, was used increasingly during the 1970's and 1980's.
28 Associated with this increasing experience was the clinical observation that there was also a risk of accumulation of morphine metabolites, particularly in the presence of renal impairment. Morphine-6-glucuronide, an analgesic metabolite, was recognized as having a useful role in enhancing analgesia. However, a number of reports have described seizures, cognitive impairment, nausea, and problems of myoclonus that were associated with accumulation of morphine-6-glucuronide.
28-35
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The potential role of morphine metabolites, in particular the ratio of 3- glucuronide to
6-glucuronide in the development of opioid-related toxicity, has been reported. The literature on this issue has been somewhat controversial. There is certainly no disagreement that morphine metabolites do increase in the presence of deteriorating renal function. However, there has been conflicting evidence regarding the role and ratios of the metabolites in patients exhibiting both a poor response to increasing morphine doses and associated toxicity.
36-40
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Route of Administration
Oral administration is preferred because it is convenient and usually inexpensive.
When patients cannot take oral medications, other less invasive (e.g., rectal or transdermal) routes should be offered. Parenteral methods should be used only when simpler, less demanding, less costly methods are inappropriate or ineffective.
In general, assessing the patient's response to several different oral opioids is advisable before abandoning the oral route in favor of anesthetic, neurosurgical, or other invasive approaches.
Rectal. Use this safe, inexpensive, effective route for delivery of opioids as well as non-opioids when patients have nausea or vomiting. Rectal administration is inappropriate for the patient who has diarrhea, anal/rectal lesions, or mucositis; who is thrombocytopenic or neutropenic; who is physically unable to place the suppository in the rectum; or who prefers other routes.
Transdermal (fentanyl). Patches currently available are formulated to provide analgesia lasting up to 72 hours. This preparation is not suitable for rapid dose titration and should be used for relatively stable analgesic requirement when rapid increases or decreases in dosage are not likely to be needed.
Intermittent injection or continuous infusion. Intravenous and subcutaneous routes provide effective opioid delivery. Methadone may cause skin irritation when infused subcutaneously or intravenously.
Intravenous administration provides a rapid onset of analgesia, but the duration of analgesia after a bolus dose is shorter than with other routes. In patients requiring continuous intravenous access for other purposes, this route of administration may be the most cost effective and provides a consistent level of analgesia. When there is no intravenous access, subcutaneous opioid infusion is a practical alternative for the home setting.
Patient-controlled analgesia (PCA). Use PCA to help the patient maintain independence and control by matching drug delivery to the need for analgesia. The opioid may be administered orally or via a dedicated portable pump to deliver the drug intravenously, subcutaneously, or intraspinally.
Intraspinal. Consider this invasive route for patients who develop intractable pain or
Florida Heart CPR* Pain Mgt in Cancer Patients

intolerable side effects with other routes. Use of the epidural or intrathecal route requires skill and expertise that may not be available in all settings. Table 6 presents the advantages and disadvantages of intraspinal administration.
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The main indication for long-term administration of intraspinal opioids is intractable pain in the lower part of the body, particularly bilateral or midline pain. Profound analgesia is possible without motor, sensory, or sympathetic blockade. Local anesthetics may be combined with opioids for intraspinal administration.
Side Effects
Clinicians who follow patients during long-term opioid treatment should watch for potential side effects and manage them as the need arises.
Constipation. Anticipate the constipating effects of analgesics. Opioids compromise gastro-intestinal tract peristaltic function (a nearly universal side effect).
Consequently, stool within the gut lumen becomes excessively dehydrated. The cornerstone of effective prophylaxis, therefore, are measurements aimed at keeping the patient well-hydrated in order to maintain well-hydrated stool. All patients using opioid medications should be prescribed a scheduled regimen of stool softening agents (e.g., docusate sodium) at the time opioid treatment commences. Patients who do not adequately respond to an aggressive regimen with stool softeners may benefit from the addition of mild osmotic agents (e.g., 70% sorbitol solution, lactulose, milk of magnesia), lubricants (e.g., mineral oil), bulk-forming laxatives
(e.g., psyllium) with appropriate orally- administered hydration, or mild cathartic laxatives (e.g., casanthrol, senna). Stimulant cathartics (e.g., senna, bisacodyl) may be useful in severely constipated patients, however, they may be relatively ineffective in situations where stool has become desiccated. (See the PDQ summary on Constipation, impaction, and bowel obstruction for more information.)
Nausea and vomiting. Treat with anti-emetics such as phenothiazines or metoclopramide. Depending on the anti-emetic chosen, monitor the patient for increased sedation.
Sedation and mental clouding. Change in mental status requires a full evaluation to exclude other treatable causes. Persistent drug-induced sedation may be treated by reducing the dose and increasing the frequency of opioid administration. CNS stimulants such as caffeine, dextroamphetamine, pemoline, and methylphenidate also help decrease opioid sedative effects.
Respiratory depression. Patients receiving long-term opioid therapy generally develop tolerance to the respiratory depressant effects of these agents. When indicated for reversal of opioid-induced respiratory depression, administer naloxone, titrated in small increments to improve respiratory function without reversing analgesia. Monitor the patient carefully until the episode of respiratory depression
Florida Heart CPR* Pain Mgt in Cancer Patients

resolves. Note that the opioid antagonists have a short half-life and may have to be given repeatedly until the agonist drug is sufficiently cleared.
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Subacute overdose. Perhaps more common than acute respiratory depression, subacute overdose may manifest as slowly progressive (hours to days) somnolence and respiratory depression. Before reducing analgesic doses, advancing disease must be considered, especially in the dying patient. Generally, withholding one or two doses of an opioid analgesic is adequate to assess whether mental and respiratory depression are opioid-related. If symptoms resolve after temporary opioid withdrawal, reduce the scheduled opioid dosage by 25 percent. If symptoms do not abate, but the patient complains of or exhibits signs of increased pain or if symptoms referable to opioid withdrawal occur, consider alternative causes for CNS depression and reinstitute analgesic treatment. Ongoing assessment is essential to maintain adequate pain relief.
Other opioid side effects. Dry mouth, urinary retention, pruritus, myoclonus, dysphoria, euphoria, sleep disturbances, sexual dysfunction, and inappropriate secretion of antidiuretic hormone are less common.
Adjuvant Drugs
Adjuvant drugs are valuable during all phases of pain management to enhance analgesic efficacy, treat concurrent symptoms, and provide independent analgesia for specific types of pain. Adjuvants include:
Corticosteroids provide a range of effects including transient mood elevation, antiinflammatory activity, antiemetic activity, and appetite stimulation and may be beneficial in the management of cachexia and anorexia. They also reduce cerebral and spinal cord edema and are essential in the emergency management of elevated intracranial pressure and epidural spinal cord compression. Corticosteroids may be useful during a pain crisis. Chronic administration increases the risk for depression, agitation, bleeding, diabetes, muscle loss, infection, and Cushing's syndrome.
Anticonvulsants are used to manage neuropathic pain, especially lancinating or burning pain. Some agents must be used with caution in cancer patients undergoing marrow-suppressant therapies, such as chemotherapy and radiation therapy.
Antidepressants, especially the tricyclics, are useful in the management of neuropathic pain. These drugs have innate analgesic properties and may potentiate the analgesic effects of opioids. The most widely reported experience has been with amitriptyline; therefore, it should be viewed as the tricyclic agent of choice. These drugs have anticholinergic side effects which may be additive to the side effects of opioids.
Neuroleptics, particularly methotrimeprazine, have been used to treat chronic pain syndromes. Methotrimeprazine lacks opioid inhibiting effects on gut motility and may
Florida Heart CPR* Pain Mgt in Cancer Patients

be useful for treating opioid-induced intractable constipation or other dose-limiting side effects. It also has anti-emetic and anxiolytic effects. Methotrimeprazine is sedating and may cause hypotension if administered by rapid intravenous injection.
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Local anesthetics have been used to treat neuropathic pain. Side effects include gastrointestinal upset; a careful cardiac evaluation is required.
Hydroxyzine is a mild anxiolytic agent with sedating properties characteristic of antihistamine (H1) agents that is useful in treating the anxious patient with pain. This antihistamine also has antipruritic properties and mild antiemetic properties.
Psychostimulants may be useful in reducing opioid-induced sedation when opioid dose adjustment (i.e., reduced dose and increased dose frequency) is not effective.
Patients should be encouraged to remain active and participate in self-care when possible. Noninvasive physical and psychosocial modalities can be used concurrently with drugs and other interventions to manage pain during all phases of treatment. The effectiveness of these modalities depends on the patient's participation and communication of which methods best alleviate pain.
Physical Modalities
Generalized weakness, deconditioning, and musculoskeletal pain associated with cancer diagnosis and therapy may be treated by:
Heat. Avoid burns by wrapping the heat source (e.g., hot pack or heating pad) in a towel. A timing device is useful to prevent burns from an electrical heating pad. The use of heat on recently irradiated tissue is contraindicated, and diathermy and ultrasound are not recommended for use over tumor sites.
Cold. Apply flexible ice packs that conform to body contours for periods not to exceed 15 minutes. Cold treatment reduces swelling and may provide longer-lasting relief than heat but should be used cautiously in patients with peripheral vascular disease and on tissue damaged by radiation therapy.
Massage, pressure, and vibration. Physical stimulation techniques have direct mechanical effects on tissues and enhance relaxation when applied gently. Tumor masses should not be aggressively manipulated. Massage is not a substitute for active exercise in ambulatory patients.
Exercise. Exercise strengthens weak muscles, mobilizes stiff joints, helps restore coordination and balance, and provides cardiovascular conditioning. Therapists and trained family or other caregivers can assist the functionally-limited patient with range-of-motion exercises to help preserve strength and joint function. During acute
Florida Heart CPR* Pain Mgt in Cancer Patients

pain, exercise should be limited to self-administered range-of-motion. Weightbearing exercise should be avoided when bone fracture is likely.
Repositioning. Reposition the immobilized patient frequently to maintain correct body alignment, to prevent or alleviate pain, and to prevent pressure ulcers.
Immobilization. Use restriction of movement to manage acute pain or to stabilize fractures or otherwise compromised limbs or joints. Use adjustable elastic or thermoplastic braces to help maintain correct body alignment. Keep joints in positions of maximal function rather than maximal range. Avoid prolonged immobilization.
14
Stimulation Techniques
Transcutaneous electrical nerve stimulation (TENS). Controlled, low-voltage electrical stimulation applied to large myelinated peripheral nerve fibers via cutaneous electrodes to inhibit pain transmission. Patients with mild to moderate pain may benefit from a trial of TENS to see if it is effective in reducing the pain.
TENS is a low-risk intervention.
Acupuncture. Pain treated by inserting small, solid needles into the skin, with or without the application of electrical current. Needle placement follows the Eastern theory of vital energy flow.
Cognitive-behavioral interventions are an important part of a multimodal approach to pain management. They help to give the patient a sense of control and to develop coping skills to deal with the disease and its symptoms. Guidelines by a National
Institutes of Health assessment panel exist suggesting integration of pharmacologic and behavioral approaches for treatment of pain and insomnia.
1
Interventions introduced early in the course of illness are more likely to succeed because they can be learned and practiced by patients while they have sufficient strength and energy. Patients and their families should be given information about and encouraged to try several strategies, and to select one or more of these cognitive-behavioral techniques to use regularly:
Relaxation and imagery. Simple relaxation techniques should be used for episodes of brief pain (e.g., during procedures). Brief, simple techniques are preferred when the patient's ability to concentrate is compromised by severe pain, a high level of anxiety, or fatigue.
Hypnosis. Hypnotic techniques may be used to induce relaxation and may be combined with other cognitive-behavioral strategies. Hypnosis is effective in relieving pain in individuals who can concentrate well, use imagery, and who are motivated to
Florida Heart CPR* Pain Mgt in Cancer Patients

practice.
Cognitive distraction and reframing. Focusing attention on stimuli other than pain or negative emotions accompanying pain may involve distractions that are internal
(e.g., counting, praying, or making self-statements such as "I can cope,"), external
(e.g., music, television, talking, listening to someone read, or the use of a visual focal point). In the related technique, cognitive reappraisal, patients learn to monitor and evaluate negative thoughts and replace them with more positive thoughts and images.
Patient education. Both oral and written information and instructions should be provided about pain, pain assessment, and the use of drugs and other methods of pain relief. Patient education should emphasize that almost all pain can be effectively managed. Major barriers to effective pain management (Table 1) should be discussed to correct patient and family misconceptions.
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Psychotherapy and structured support. Some patients benefit from short-term psychotherapy provided by trained professionals. Patients whose pain is particularly difficult to manage and who develop symptoms of clinical depression or adjustment disorder should be referred to a psychiatrist for diagnosis. The relationship between poorly controlled pain, depression, and thoughts of suicide should not be ignored.
Support groups and pastoral counseling. Because many patients benefit from peer support groups, clinicians should be aware of locally active groups and offer this information to patients and their families. Pastoral counseling members of the health care team should participate in meetings to discuss patients' needs and treatment.
They should be a source of information on community resources for spiritual care and social support.
Radiation Therapy
Local or whole-body radiation enhances the effectiveness of analgesic drug and other noninvasive therapy by directly affecting the cause of pain (i.e., reducing primary and metastatic tumor bulk). Dosage must be chosen to achieve a balance between the amount of radiation required to kill tumor cells and that which would adversely affect normal cells or allow the repair of damaged tissue.
A single intravenous injection of beta particle-emitting agents such as iodine-131, phosphorus-32-orthophosphate, and strontium-89, as well as the investigational new drugs rhenium-186 and samarium-153, can relieve pain of widespread bony metastases. Half the patients so treated respond to a second treatment if pain recurs.
Florida Heart CPR* Pain Mgt in Cancer Patients

Surgery
Curative excision or palliative debulking of a tumor has potential to reduce pain directly, relieve symptoms of obstruction or compression, and improve prognosis, even increasing long-term survival. Oncologic surgeons and other health care providers should be familiar with the interactions of chemotherapy, radiation therapy, and surgical interventions to avoid or anticipate iatrogenic complications. They should also recognize characteristic pain syndromes that follow specific surgical procedures.
Invasive Interventions
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Less invasive analgesic approaches should precede invasive palliative approaches.
However, for a minority of patients in whom behavioral, physical, and drug therapy do not alleviate pain, invasive therapies are useful.
Nerve Blocks
Control of otherwise intractable pain can be achieved by the application of a local anesthetic or neurolytic agent. Nerve blocks are performed for several reasons:
Diagnostic -- to determine the source of pain (e.g., somatic versus sympathetic pathways)
Therapeutic -- to treat painful conditions that respond to nerve blocks (e.g., celiac block for pain of pancreatic cancer)
Prognostic -- to predict the outcome of long-lasting interventions (e.g., infusions, neurolysis, rhizotomy)
Preemptive -- to prevent pain following procedures
A single injection of a nondestructive agent such as lidocaine or bupivacaine, alone or in combination with an anti-inflammatory corticosteroid for a longer-lasting effect, can provide local relief from nerve or root compression. Placement of an infusion catheter at a sympathetic ganglion extends the sympathetic blockade from hours to days or weeks. Destructive agents such as ethanol or phenol can be used to effect neurolysis at sites identified by local anesthesia as appropriate for permanent pain relief, and may also be used to cause destruction of central nervous system structures.
Neurologic Interventions
Neurosurgery can be performed to implant devices to deliver drugs or to electrically stimulate neural structures. Surgical ablation of pain pathways should, like neurolytic blockade, be reserved for situations in which other therapies are ineffective or poorly tolerated. In general, the choice of neurosurgical procedure is based on location and type of pain (somatic, visceral, deafferentation), the patient's general condition
Florida Heart CPR* Pain Mgt in Cancer Patients

and life expectancy, and the expertise and follow-up available.
Management of Procedural Pain
Many diagnostic and therapeutic procedures are painful to patients. Treat anticipated procedure-related pain prophylactically and integrate pharmacologic and nonpharmacologic interventions in a complementary style.
Use local anesthetics and short-acting opioids to manage procedure-related pain, allowing adequate time for the drug to achieve full therapeutic effect. Anxiolytics and sedatives may be used to reduce anxiety or to produce sedation.
Cognitive-behavioral interventions, such as imagery or relaxation, are useful in managing procedure-related pain and anxiety. Examples of relaxation exercises are provided in the section "Assessment and Management Tools." Patients generally tolerate procedures better when they are informed of what to expect.
Offer the option for a relative or friend to accompany the patient for support.
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Patients and families may have difficulty remembering details of the pain management plan. Therefore, they should be given a written pain management plan. The patient and family should receive clear instructions regarding telephone contact for more urgent questions relating to pain management.
Like other adults, elderly patients require comprehensive assessment and aggressive management of cancer pain. However, older patients are at risk for undertreatment of pain because of underestimation of their sensitivity to pain, the expectation that they tolerate pain well, and misconceptions about their ability to benefit from the use of opioids. Issues in assessing and treating cancer pain in older patients include:
Multiple chronic diseases and sources of pain. Age and complex medication regimens place them at increased risk for drug-drug and drug-disease interactions.
Visual, hearing, motor, and cognitive impairments. The use of simple descriptive, numeric, and visual analog pain assessment instruments may be impeded.
Cognitively impaired patients may require simpler scales and more frequent pain assessment.
NSAID side effects. Although effective alone or as adjuncts to opioids, NSAIDs are more likely to cause gastric and renal toxicity and other drug reactions such as cognitive impairment, constipation, and headaches in older patients. Alternative
Florida Heart CPR* Pain Mgt in Cancer Patients

NSAIDs (e.g., choline magnesium trisalicylate) or co-administration of misoprostol with NSAIDs should be considered to reduce gastric toxicity.
Opioid effectiveness. Older persons tend to be more sensitive to the analgesic and
CNS depressant effects of opioids. Peak opioid effects are generally greater and the duration of pain relief may be longer.
Patient-controlled analgesia. Slower drug clearance and increased sensitivity to undesirable drug effects (e.g., cognitive impairment) indicate the need for cautious initial dosing and subsequent titration and monitoring of continuous parenteral infusions.
Alternative routes of administration. Although useful for patients who have nausea or vomiting, the rectal route may be inappropriate for elderly or infirm patients who are physically unable to place the suppository in the rectum.
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Postoperative pain control. Following surgery, surgeons and other health care team members should maintain frequent direct contact with the elderly patient to reassess the quality of pain management.
Change of setting. Reassessment of pain management and appropriate changes should be made whenever the elderly patient moves (e.g., from hospital to home or nursing home).
1. Bruera E, Schoeller T, Fainsinger RL, et al.: Custom-made suppositories of methadone for severe cancer pain. Journal of Pain and Symptom Management 7(6):
372-374, 1992.
2. Hunt G, Bruera E: Respiratory depression in a patient receiving oral methadone for cancer pain. Journal of Pain and Symptom Management 10(5): 401-404, 1995.
3. Crews JC, Sweeney NJ, Denson DD: Clinical efficacy of methadone in patients refractory to other mu-opioid receptor agonist analgesics for management of terminal cancer pain: case presentations and discussion of incomplete crosstolerance among opioid agonist analgesics. Cancer 72(7): 2266-2272, 1993.
4. Sjogren P, Jensen NH, Jensen TS: Disappearance of morphine-induced hyperalgesia after discontinuing or substituting morphine with other opioid agonists.
Pain 59(2): 313-316, 1994.
5. Leng G, Finnegan MJ: Successful use of methadone in nociceptive cancer pain unresponsive to morphine. Palliative Medicine 8(2): 153-155, 1994.
6. Thomas Z, Bruera E: Use of methadone in a highly tolerant patient receiving parenteral hydromorphone. Journal of Pain and Symptom Management 10(4): 315-
317, 1995.
7. Manfredi PL, Borsook D, Chandler SW, et al.: Intravenous methadone for cancer pain unrelieved by morphine and hydromorphone: clinical observations. Pain 70(1):
99-101, 1997.
Florida Heart CPR* Pain Mgt in Cancer Patients

8. Bruera E, Watanabe S, Fainsinger RL, et al.: Custom-made capsules and suppositories of methadone for patients on high-dose opioids for cancer pain. Pain
62(2): 141-146, 1995.
9. Bruera E, Pereira J, Watanabe S, et al.: Opioid rotation in patients with cancer pain: a retrospective comparison of dose ratios between methadone, hydromorphone, and morphine. Cancer 78(4): 852-857, 1996.
10. Vigano A, Fan D, Bruera E: Individualized use of methadone and opioid rotation in the comprehensive management of cancer pain associated with poor prognostic indicators. Pain 67(1): 115-119, 1996.
11. Mercadante S, Sapio M, Serretta R, et al.: Patient-controlled analgesia with oral methadone in cancer pain: preliminary report. Annals of Oncology 7(6): 613-617,
1996.
12. Watanabe S, Belzile M, Kuehn N, et al.: Capsules and suppositories of methadone for patients on high-dose opioids for cancer pain: clinical and economic considerations. Cancer Treatment Reviews 22(Suppl. A): 131-136, 1996.
13. Fainsinger R, Schoeller T, Bruera E: Methadone in the management of cancer pain: a review. Pain 52(2): 137-147, 1993.
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Florida Heart CPR* Pain Mgt in Cancer Patients

1. Barriers (related to health care professionals) to cancer pain management may include: a. Fear of patient addiction b. Poor assessment of pain c. Inadequate knowledge of pain management d. All of the above
2. Initial assessment of pain should include: a. Detailed history b. Physical examination c. Psychosocial assessment d. All of the above
3. The mainstay of pain assessment is the a.
Diagnostic evaluation b.
Psychosocial assessment c.
Physical examination d.
Patient self-report
4. ______ assessment of cancer pain is crucial. a.
Thorough b.
Initial c.
Critical d.
Continual
5. Adverse side effects from NSAIDs include: a. Renal failure b. Hepatic dysfunction c. Gastric ulceration d. All of the above
6. The most commonly used opioid is a. Methadone b. Warfarin c. Morphine d. Buprenorphine
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Florida Heart CPR* Pain Mgt in Cancer Patients

7. Intravenous administration provides a rapid onset of analgesia. The duration of analgesia after a bolus dose is ______ other routes. a.
Longer than with b.
Shorter than with c.
Comparable to d.
Extremely long
8. Analgesics can cause: a.
Constipation b.
Respiratory compression c.
Sedation and mental clouding d.
All of the above
9. Adjuvant drugs are valuable during all phases of pain management to a.
enhance analgesic efficacy b.
treat concurrent symptoms c.
provide independent analgesia for specific types of pain d.
all of the above
10. An example of an adjuvant drug would be a. Corticosteroids b. Morphine c. Anticonvulsants d. A and C
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Florida Heart CPR* Pain Mgt in Cancer Patients