Managing pain
From the December ACP Observer, copyright © 2004 by the American College of Physicians.
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The World Health Organization (WHO) has published a simple and validated three-step approach to pain management (see "WHO Analgesic Ladder
"). The basic principles behind the ladder's several steps include selecting the appropriate analgesic for pain intensity and individualizing the dose by titration of opioid analgesics.
According to the WHO ladder, mild pain—the lowest step—can be treated with nonopioid drugs alone.
Moderate pain can be treated with nonopioid analgesics in combination with low-dose opioid drugs. And severe pain is treated with nonopioid drugs in combination with higher-dose opioids. At any step on the ladder, adjuvant therapy may be useful.
Pain intensity scales are used to categorize pain as mild, moderate or severe and to assess the effects of a treatment regimen in order to titrate the analgesic dose.
Treating mild pain
Mild pain ranks as 1-3 on a 0-10 pain intensity scale. Mild pain can usually be adequately treated with aspirin, acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs).
These drugs differ from opioids in two key ways: Analgesia has a ceiling effect, so greater amounts of the drug are not associated with greater pain control; and they do not produce tolerance or physical dependence. Unless contraindicated, management of all levels of pain includes a drug from this category, even if the pain is moderate to severe and requires adding an opioid. Some drugs in this category are available in parenteral and rectal forms.
Aspirin is a useful nonopioid analgesic with a predictable side-effect profile. The two most common side effects are gastric disturbances—such as nausea, dyspepsia, abdominal pain and ulceration—and bleeding diathesis. Aspirin hypersensitivity does occur and may present with rhinitis and asthma or with urticaria, wheals, angioneurotic edema and hypotension. Patients who are sensitive to aspirin may also be sensitive to NSAIDs, and aspirin should not be used in children because of the possible association with Reye's syndrome.
Acetaminophen is similar to aspirin in its analgesic effect but lacks the gastric and bleeding side effects. However, overdosage with acetaminophen can cause hepatic necrosis in normal individuals in doses over 4 grams per day. Lesser dosages, but well within the therapeutic range, can cause hepatic necrosis in high-risk individuals, who include heavy alcohol drinkers, patients with liver disease and fasting patients.
The analgesic efficacy of NSAIDs ranges from equivalent to somewhat superior to aspirin. Like aspirin, NSAIDs inhibit platelet aggregation—but unlike aspirin, the effect is reversible and lasts only as long as there is an effective serum drug concentration.
NSAIDs are also associated with gastrointestinal disturbances that range from nausea and pain to gastric bleeding and perforation.
Previous meta-analyses have suggested that low-dose ibuprofen (under 1.6 gram per day) may have the lowest gastric risk. Aspirin, indomethacin, naproxen and sulindac have an intermediate risk; and tolmetin, ketoprofen and piroxicam have the highest risk. High-dose ibuprofen is associated with an intermediate risk of gastric complications.
Based on these results, pain management experts recommend using the lowest-risk drugs at the lowest possible dose needed to control pain. Prophylactic use of proton pump inhibitors, histamine 2 blockers and misoprostol have been recommended for individuals at high risk for gastric complications.
Lately, selective COX-2 inhibitors have been used to treat chronic pain in individuals at high risk. The selective inhibition of the enzyme cyclooxygenase 2 produces the desired therapeutic effect while minimizing adverse effects on the stomach and kidneys. This advantage, however, becomes less prominent with long-term COX-2 use.
Earlier this year, the COX-2 inhibitor rofecoxib was withdrawn from the worldwide market due to the drug's increased risk of cardiovascular events among patients taking it for more than 18 months. While there is no evidence that another COX-2, celecoxib, also increases risk, celecoxib's manufacturer has announced that a large controlled trial will begin next year to study the drug's effect in osteoarthritis patients with recent myocardial infarctions.
NSAIDs are also associated with liver damage and are not recommended for patients with liver disease. Prudent practice would include monitoring of transaminase levels of patients taking chronic NSAIDs.
Treating moderate and severe pain
Moderate pain ranks between 4-6 on the 0-10 pain intensity scale.
When treating moderate pain, add low-dose opioid drugs to aspirin, acetaminophen or NSAID regimens. For patient convenience, many opioids are marketed as combination products containing one of these agents.
The daily cumulative acetaminophen dose will limit opioid dosing in combination medication. For this reason, separate dosing of the opioid and acetaminophen is preferred, particularly when titrating the opioid dose.
Patients taking chronic opioids have incomplete cross-tolerance to side effects. You must take this into account when changing from one opioid to another by reducing the dose of the new opioid and providing careful follow-up. (See "Equianalgesic dosing" and the "Dosing and conversion chart for opioid analgesics.")
Severe pain ranks as 7-10 on the 0-10 pain intensity scale.
Treating severe pain requires higher-dose opioid drugs, while continuing aspirin, acetaminophen or NSAIDs as coanalgesics is recommended. At any of the steps in the WHO Analgesic Ladder, adjuvant therapy may provide additional relief.
Adjuvant therapy
A number of drug and nondrug therapies can help enhance the effects of nonopioid and opioid analgesics.
Tricyclic antidepressants are at the top of the list. Studies have confirmed their effectiveness in treating diabetic neuropathy and postherpetic neuralgia, and they are frequently used for neuropathic pain from other sources.
The effective analgesic dose of tricyclic antidepressants is lower than the typical antidepressant dose. Limiting side effects are related to their anticholinergic properties and include dry mouth, urinary retention, constipation, delirium, sedation, orthostatic hypotension and blurred vision.
Tricyclic antidepressants should be used with caution, if at all, in patients with coronary artery disease, and they are contraindicated in patients with electrical conduction blocks. Because of their sedating properties, these drugs can be used to enhance sleep if the entire dose is taken at bedtime.
Anticonvulsant medications can relieve the shooting, electrical pains of peripheral nerve dysfunction.
Clinical trials have demonstrated the drugs' effectiveness in diabetic neuropathy, postherpetic neuralgia and trigeminal neuralgia. While very few trials studied the use of these drugs in cancer pain, they are often used to treat peripheral nerve syndromes caused by malignancies.
At doses of 65 mg or greater, caffeine can augment the effect of aspirin. The optimal dose is unknown but a commonly accepted range is between 65-200 mg/day.
Corticosteroids, which can reduce edema and lyse certain tumors, can enhance the analgesic effect of nonopioid and opioid drugs. They may be particularly effective in managing malignant infiltration of brachial and lumbar plexus, spinal cord compression and headache pain due to brain tumors.
Chronic use is associated with the development of Cushing's syndrome, myopathy and possibly an increased risk of gastrointestinal bleeding.
Psychostimulants such as methylphenidate and dextroamphetamine may enhance the analgesic effect of opioids, but they have not been thoroughly studied in cancer pain. Psychostimulants are used most frequently to counteract the opioids' sedating effects.
Non-drug adjuvant therapy
Thermal, electrical and mechanical modalities have long been used to manage pain.
Electrical impulses applied to peripheral nerves through transcutaneous electrical nerve stimulation can reduce subjective reports of nociceptive and neuropathic pain. The benefit of stimulation is mediated through the induction of endogenous opioids and the preferential transmission of benign tactile impulses in second-order processing.
Heat and cold—which reduce muscle spasm, inflammation and the transmission of pain stimuli—are invaluable adjuncts to pharmacologic and therapeutic interventions. Massage, relaxation and biofeedback have also become part of mainstream adjunctive pain management practice, bringing significant benefits to appropriate patients.
Key points for treating mild pain
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Start therapy with aspirin, acetaminophen or a nonsteroidal anti-inflammatory drug (NSAID).
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Aspirin, NSAIDs and acetaminophen have a ceiling effect. Increasing the dose does not increase the therapeutic effect but does increase the toxic effect.
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Use caution when prescribing NSAIDs for elderly patients and individuals with renal failure, bleeding tendencies, gastric ulceration and hepatic dysfunction.
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Acetaminophen may be the drug of choice for musculoskeletal pain (particularly in elderly patients) and in patients at risk for side effects of aspirin and NSAIDs.
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Acetaminophen dose should not exceed 4 grams per day and should be less for elderly patients, those with liver disease and patients who regularly consume alcohol.
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Prescribe nonopioid analgesics around the clock—not on an "as-needed" basis—for persistent, chronic pain.
When switching opioids, you should follow these five steps:
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Add the total dose of each opioid given during 24 hours. If both parenteral and oral doses were given, calculate the 24-hour total for each.
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Determine the conversion ratio for each type of opioid and each route by using the "Dosing and conversion chart for opioid analgesics." Calculate the conversion ratio as the equianalgesic dose of the current opioid (or route) divided by the equianalgesic dose of the alternative opioid (or route).
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Divide the 24-hour dose of the current opioid (or route) by the conversion ratio to estimate the 24-hour dose of the alternative opioid (or route).
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Modify this estimate based upon the clinical situation.
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Divide the estimated dose by the appropriate dosing interval for the appropriate opioid (or route) based upon the "Dosing and conversion chart for opioid analgesics
."
See "Clinical exercises."
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