Instructions: Spend 5 minutes reviewing the case below and considering the questions that follow. Case Study 4
Samuel is a 94-year-old man in the late stages of metastatic prostate cancer. The cancer was initially treated 16 years earlier with a radical prostatectomy and adjuvant radiation therapy, but it has recurred with infiltration to his pelvic bones. He has been under home hospice care for the past month. His pain is being treated with transdermal fentanyl which has reduced the nausea he was experiencing with oral ER/LA oxycodone. Now, however, he says he often feels “fuzzy” and “out of it” to the point that he can’t remember conversations he has had with his wife or daughter. On a visit by the hospice nurse, Sam complains about this, saying “I want to be able to say goodbye to people, and thank them, but I just feel like a zombie half the time.”
1. How might Sam’s competing desires for pain relief and mental clarity be addressed?
2. Are there any alternative pharmacological or non-pharmacological analgesic options that might be appropriate for Sam?
3. What other types of health care professionals might be called on to help Sam achieve the kinds of end-of-life communication he desires?
In such cases, using a pure opioid may be preferable. (Single-agent formulations are available for many types of opioids, such as morphine, oxycodone, and hydromorphone.) The FDA has limited to 325 mg the amount of acetaminophen allowed in prescription opioid combination products in an attempt to limit liver damage and other ill effects primarily due to excessive doses of combined products. 51 Contraindications for NSAIDs include decreased renal function (relatively common at the end of life) and liver failure. Platelet dysfunction or other potential bleeding disorders, common due to cancer or its treatment, are also contraindications to non- selective NSAIDS because of their inhibitory effects on platelet aggregation, with resultant prolonged bleeding time. 52 Concurrent use of anticoagulants (Coumadin for example) is also a contraindication. Proton pump inhibitors or misoprostol may be considered to prevent GI bleeding. 53 Attention has recently been focused on the potential limited efficacy of acetaminophen in older patients. Although it has been considered a viable co-analgesic with opioids, and to be first-line therapy in elderly patients with musculoskeletal pains or pain associated with osteoarthritis, the relative limited efficacy and significant adverse effects of this agent, particularly hepatic and renal toxicity, have raised concerns. 54 Reduced doses of 2000 mg/day or the avoidance of acetaminophen is recommended in the face of renal insufficiency or liver failure, and particularly in individuals with a history of significant alcohol use. 55 Adjuvant Analgesics Although opioid medications are a mainstay of pain management at the end-of-life, many other classes of medications have proven effective and, in some cases, preferable to opioids (see Table 6).
Some exert a direct analgesic effect mediated by non-opioid receptors centrally or peripherally. Other adjuvant “analgesics” have no direct analgesic qualities but may provide pain relief indirectly by affecting organs or body systems involved in painful sensations. Some antidepressant agents appear to exert analgesic properties and may be particularly helpful for neuropathic pain conditions. Tricyclic antidepressants inhibit reuptake of norepinephrine and serotonin, which appears to exert analgesic effects, either directly or indirectly. These agents have been shown to provide clinically relevant effects in a review of analgesic studies conducted in neuropathic pain conditions, primarily diabetic neuropathy and other non-cancer conditions. 57 Potential side effects include cardiac arrhythmias, conduction abnormalities, narrow-angle glaucoma, and clinically significant prostatic hyperplasia. On the other hand, the sleep-enhancing and mood- elevating effects of these antidepressants may benefit some patients. Although little evidence supports an analgesic effect for SSRIs, some newer antidepressants, such as the serotonin-norepinephrine reuptake inhibitors have been shown to be effective in relieving neuropathic pain, including venlafaxine and duloxetine. 58 These have the added advantage of alleviating hot flashes, a common and disturbing symptom, particularly in breast cancer patients undergoing hormonal therapy. Care must be taken in such situation, however, because duloxetine reduces the bioavailability of tamoxifen, potentially reducing its therapeutic efficacy. 59 The anti-epilepsy drugs gabapentin and pregabalin have undergone extensive testing in many non-cancer neuropathy syndromes, and a recent review concluded that these drugs have a clinically meaningful effect. 57
The most common adverse effects reported by patients are dizziness; some patients also develop fluid retention. Although the data for the efficacy of other anticonvulsants are not as conclusive as those for gabapentin and pregabalin, existing reports suggest potential efficacy. As with most adjuvant analgesics, antiepileptic agents are commonly used in combination with opioid therapy, particularly when pain is moderate to severe. A review of cancer trials found that adjuvant analgesics added to opioids provide additional relief, usually within 4 to 8 days, with the strongest evidence for gabapentin. 60 Corticosteroids can play a valuable role in treating end-of-life pain related to neuropathic pain syndromes, pain associated with stretching of the liver capsule due to metastases, for treating bone pain (due to their anti-inflammatory effects) as well as for relieving malignant intestinal obstruction. 61 Dexamethasone produces the least amount of mineralocorticoid effect and is available in a variety of delivery forms, including oral, intravenous, subcutaneous, and epidural. 41 Local anesthetics may be useful in preventing procedural pain and in relieving neuropathic pain. Local anesthetics can be given topically, intravenously, subcutaneously, or intraspinally. Both gel and patch versions of lidocaine have been shown to reduce the pain of postherpetic neuralgia and cancer-related neuropathic pain. 62 Intravenous or subcutaneous lidocaine at 1 to 5 mg/kg administered over 1 hour, followed by a continuous infusion of 1 to 2 mg/kg/hour, has been reported to reduce intractable neuropathic pain in patients in inpatient palliative care and home hospice settings. 63
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