Initial Assessment

The goal of the initial assessment of pain is to characterize the pain by location, intensity, and etiology. Essential to initial assessment are:

• Detailed history.
• Physical examination.
• Psychosocial assessment.
• Diagnostic evaluation.

Patient Self-Report

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. Examples of simple self-report pain intensity scales include the simple descriptive, numeric, and visual analogue scales shown on page 23.
• 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. See the sample pain history form on pages 24-25.
• Intensity or severity. Encourage the patient to keep a log of pain intensity scores to report during followup visits or by telephone.
• Aggravating and relieving factors. Ask when the patient experiences the most pain and the least pain. Document responses in the patient's chart.
• 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 (as scores on a pain scale) in the patient's pain history.

Figure

Figure 4. Pain intensity scale.

Box

Figure 5. Brief Pain Inventory (Short Form). Study ID#_________________ Hospital#________________ Do not write above this line Date:____/____/____ Time:______________ Name:______________________________________________________ (more...)

Followup Assessment

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.

Acetaminophen and NSAIDs

NSAIDs are effective for relief of mild pain, and 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. Do not use NSAIDs in patients with thrombocytopenia. 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:

  • Renal failure.
  • Hepatic dysfunction.
  • Bleeding.
  • Gastric ulceration.

Table

Table 3. Dosing data for acetaminophen and NSAIDs.

Because both NSAIDs and other drugs (e.g., coumadin, methotrexate, digoxin, cyclosporin, oral antidiabetic agents, and sulfa drugs) are highly protein bound, there is potential for altered efficacy or toxicity when given simultaneously.

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 serious side effects. The clinician's ethical duty -- to benefit the patient by relieving pain -- supports increasing doses, even at the risk of side effects. Because many patients with cancer pain become opioid tolerant during long-term opioid therapy, the clinician's fear of shortening life by increasing opioid doses is usually unfounded.

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 based on a more detailed discussion contained in the Guideline.

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.

• Opioids. The most commonly used opioid, morphine, is readily available in several forms, including sustained-acting (8-12 hours) tablets of morphine. Another opioid is available as long-acting (2-3 days) transdermal fentanyl patches.
• 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 route in favor of another. Patients receiving opioid analgesics "by the clock" should be provided oral or parenteral rapid-onset short-duration opioid agonists for breakthrough pain.
• Meperidine (Demerol). Useful for brief courses (few days) to treat acute pain, meperidine generally should be avoided in treating cancer pain due to its short duration of action (2.5-3.5 hours) and its toxic metabolite, normeperidine. Accumulation of this metabolite, particularly when renal function is impaired, causes central nervous system stimulation that may lead to seizures.

Partial agonists, such as buprenorphine, have less effect than full agonists at the opioid receptor. 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. As patients develop opioid tolerance, they require more frequent dosing. 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.
• Route conversion. When changing from the oral to the rectal route, begin with the oral dose, then titrate upward frequently and carefully. Lower doses are required for parenteral routes but are similar for 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. The Guideline gives specific instructions for opioid use in elderly, children, persons physically or cognitively impaired, and known or suspected drug abusers.

Table

Table 4. Dose equivalents for opioid analgesics in opioid-naive adults and children >= 50 kg body weight[1].

Table

Table 5. Dose equivalent for opioid analgesics for opioid-naive adults <50 Kg Body Weight.

Route of Administration

Oral administration is preferred because it is convenient and usually cost-effective. 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. Assessing the patient's response to several different oral opioids is usually 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). This route is not suitable for rapid dose titration. Hence, use this route for relatively stable pain when rapid increases or decreases in intensity are not likely.
• Injection or infusion. Intravenous and subcutaneous routes provide effective opioid delivery. Avoid the intramuscular route because of unreliable absorption, pain, and inconvenience. Intravenous administration provides the most 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 opioid infusion is cost effective and provides a consistent level of analgesia. When intravenous access is not feasible, subcutaneous opioid infusion is practical in the hospital or home.
• 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 epidurally (intraspinally).
• Intraspinal. Consider this invasive route for patients who develop intractable pain or intolerable side effects with other routes. Use of this route requires skill and expertise that may not be available in all settings. Table 6 presents the advantages and disadvantages of intraspinal administration. 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.

Table

Table 6. Advantages and disadvantages of intraspinal drug delivery systems.

Drugs and Routes Not Recommended

Table 7 presents data on drugs and routes of administration not recommended for the management of cancer pain.

Table

Table 7. Drugs and routes of administration not recommended for treatment of cancer pain.

Side Effects

Clinicians who follow patients during long-term opioid treatment should watch for potential side effects and use adjuvant agents to counteract them.

• Constipation.Treat constipation (an inevitable side effect) prophylactically with dietary fiber or regularly scheduled doses of mild laxative. Severe constipation may require treatment with a stimulating cathartic, (e.g., bisadocyl, standardized senna concentrate, or hyperosmotic agents, orally or via suppository).
• 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.When possible, treat persistent drug-induced sedation 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 resolves.
• Subacute overdose.Far more common than acute respiratory depression, subacute overdose manifests as slowly progressive (hours to days) somnolence and respiratory depression. Withhold one or two doses until the symptoms have resolved, then reduce the standing dose by 25 percent.
• Other opioid side effects.Dry mouth, urinary retention, pruritis, myoclonus, altered cognitive function, dysphoria, euphoria, sleep disturbances, sexual dysfunction, physiologic dependence, tolerance, and inappropriate secretion of antidiuretic hormone.

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 mood elevation, anti-inflammatory 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.
• Anticonvulsants are used to manage neuropathic pain, especially lancinating or burning pain. Use with caution in cancer patients undergoing marrow-suppressant therapies, such as chemotherapy and radiation therapy.
• Antidepressants are useful in pharmacologic 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.
• Neuroleptics, particularly methotrimeprazine, have been used to treat chronic pain syndromes. Methotrimeprazine lacks opioid inhibiting effects on gut motility and may be useful for treating opioid-induced intractable constipation or other dose-limiting side effects. It also has anti-emetic and anxiolytic effects.
• Local anesthetics have been used to treat neuropathic pain. Side effects for these may be greater than with other drugs used to treat neuropathic pain.
• Hydroxyzine is a mild anxiolytic agent with sedating and analgesic properties that is useful in treating the anxious patient with pain. This antihistamine also has 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.

Placebos should not be used in the management of cancer pain.

Physical Modalities

Generalized weakness, deconditioning, and aches and pains associated with cancer diagnosis and therapy may be treated by:

• Cutaneous stimulation. Noninvasive techniques that can be taught to the patient or family caregiver include
• Heat. Avoid burns by wrapping the heat source (e.g., hot pack or heating pad) in a towel. The use of heat on 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 provides longer-lasting relief than heat but should not be used in patients with peripheral vascular disease or on tissue damaged by radiation therapy.
• Massage, pressure, and vibration. These methods, which help the patient through distraction or relaxation, sometimes increase pain before relief occurs. Massage should not be substituted for exercise in ambulatory patients.
• Exercise. Useful in treating subacute and chronic pain, exercise strengthens weak muscles, mobilizes stiff joints, helps restore coordination and balance, enhances patient comfort, 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 pain, exercise should be limited to self-administered range-of-motion. Weight-bearing exercise should be avoided when bone fracture is likely.
• Repositioning. Reposition the immobilized patient frequently to maintain correct body alignment and prevent or alleviate pain and, possibly, 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.
• Counterstimulation.

  • Transcutaneous electrical nerve stimulation (TENS). Controlled, low-voltage electrical stimulation applied to large myelinated peripheral nerve fibers via cutaneous electrodes to inhibit pain transmission. Although part of the efficacy of TENS can be attributed to a placebo effect, patients with mild pain may benefit from a trial of TENS to see if it is effective in reducing the pain.
  • Acupuncture. Pain treated by inserting small, solid needles into the skin. Because pain can signal disease progression, infection or treatment complication, patients who choose acupuncture should be encouraged to report new pain problems to their health care team before using this means of pain relief.

Cognitive-Behavioral Interventions

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 pain.

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 (see examples on pages 26-27) should be used for episodes of brief pain (e.g., during procedures). Brief, simple techniques such as those shown should be used when the patient's ability to concentrate is compromised by severe pain, a high level of anxiety, or fatigue.
• 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 exercises (e.g., rhythmic massage or 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 misconceptions.
• Psychotherapy and structured support. Some patients benefit from short-term psychotherapy provided by professionals with training in psychotherapy. Patients whose pain is particularly difficult to manage (e.g., substance abusers) and those who develop symptoms of clinical depression or another adjustment disorder should be referred to professionals with training in psychotherapy. 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 the support of patients and their families.

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.

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.

Nerve Blocks

Control of otherwise intractable pain can be achieved by the relatively brief application of a local anesthetic or neurolytic agent. In the management of cancer pain, 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 painful sequelae of procedures that may cause phantom limb, causalgia, or reflex sympathetic dystrophy.

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 peripheral neurolysis at sites identified by local anesthesia as appropriate for permanent pain relief.

Neurosurgery

Ablation of pain pathways should, like neurolytic blockade, be reserved for situations in which other therapies are ineffective or poorly tolerated. Neurosurgery can be performed to implant devices to deliver drugs or to electrically stimulate neural structures. The Guideline provides a list of indications for specific procedures. In general, the choice of neurosurgical procedure is based on location and type of pain (somatic, visceral, deafferentation), the patient's general condition and life expectancy, and the expertise and followup 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. Massage, pressure, or vibration may also aid relaxation. Examples of relaxation exercises are provided on pages 26-27. Applications of heat or cold may be useful in managing pain due to inflammation.

Offer the option for a relative or friend to accompany the patient for support.