Palliative Care and Pain Management at the End of Life ___________________________________________
NSAIDs are most effective for pain associated with inflam- mation. Among the commonly used NSAIDs are ibuprofen (Motrin, Advil), naproxen (Aleve, Naprosyn), and indometha- cin (Indocin). There are several classes of NSAIDs, and the response differs among patients; trials of drugs for an individ- ual patient may be necessary to determine which drug is most effective [67]. NSAIDs inhibit platelet aggregation, increasing the risk of bleeding, and also can damage the mucosal lining of the stomach, leading to gastrointestinal bleeding. There is a ceiling effect to the nonopioid analgesics; that is, there is a dose beyond which there is no further analgesic effect. In addition, many side effects of nonopioids can be severe and may limit their use or dosing. Moderate pain (Step 2) has often been treated with analgesic agents that are combinations of acetaminophen and an opioid, such as codeine, oxycodone, or hydrocodone. However, it is now recommended that these combination drugs be avoided, as limits on the maximum dose of acetaminophen limits the use of a combination drug [206; 223]. Individual drugs in combination is preferred, allowing for increases in the dose of the opioid without increasing the dose of the co-analgesic. Strong opioids are used for severe pain (Step 3). Guidelines sug- gest that the most appropriate opioid dose is the dose required to relieve the patient’s pain throughout the dosing interval without causing unmanageable side effects [187; 206; 246]. Morphine, buprenorphine, oxycodone, hydromorphone, fentanyl, and methadone are the most widely used Step 3 opi- oids in the United States. Unlike nonopioids, opioids do not have a ceiling effect, and the dose can be titrated until pain is relieved or side effects become unmanageable. For an opioid- naïve patient or a patient who has been receiving low doses of a weak opioid, the initial dose of a Step 3 opioid should be low, and, if pain persists, the dose may be titrated up daily until pain is controlled. Opioid-naïve patients are those who are not receiving opioid analgesic daily and therefore have not developed significant tolerance. Opioid-tolerant patients are those who have been taking an opioid analgesic daily for at least one week. The FDA identifies tolerance as receiving at least 60 mg of morphine daily, 30 mg of oral oxycodone daily, 8 mg of oral hydromorphone daily, or an equianalgesic dose of another opioid for one week or longer [187]. Typical starting doses for patients who are opioid-naïve have been noted, but these doses should be used only as a guide, and the initial dose, as well as titrated dosing, should be done on an individual basis ( Table 8 ). The most serious potential adverse effect following initiation of opioids for treatment of pain is oversedation followed by respiratory depression. To mitigate this risk, clinicians should discuss the role of naloxone administration by caregivers in the event of sedation/respiratory depression and make naloxone available as indicated or as required by local regulations [187]. When initiating morphine, or any opioid agent for treatment of moderate/severe pain, the prescribing clinician should consider lower starting dose titration in frail or older patients and in any patient with renal insufficiency (reduced creatinine clearance).
More than one route of opioid administration will be needed by many patients during end-of-life care, but in general, opioids should be given orally, as this route is the most convenient and least expensive. The transdermal route is preferred to the parenteral route, although dosing with a transdermal patch is less flexible and so may not be appropriate for patients with unstable pain [223]. Intramuscular injections should be avoided because injections are painful, drug absorption is unreliable, and the time to peak concentration is long [223]. Morphine is considered to be the first-line treatment for a Step 3 opioid [206]. Morphine is available in both immediate-release and sustained-release forms, and the latter form can enhance patient compliance. The sustained-release tablets should not be cut, crushed, or chewed, as this counteracts the sustained- release properties. Morphine should be avoided in patients with severe renal failure [214]. Buprenorphine (Butrans) has the general structure of mor- phine but differs from it in several ways [250]. The transdermal formulation of the drug was approved in 2010 for moderate-to- severe chronic pain in patients requiring an around-the-clock opioid for an extended period [223]. It may be used for people with renal impairment but is contraindicated in patients who have substantial respiratory depression [247; 250]. The sustained-release form of oxycodone (OxyContin) has been shown to be as safe and effective as morphine for cancer-related pain, and it may be associated with less com- mon side effects, especially hallucinations and delirium [251]. Oxycodone is also available in an immediate-release form (Roxicodone). Oxycodone should be used in people with advanced chronic kidney disease only if alternative options are not available [214]. If the drug must be used, the intervals between doses should be increased, and the patient should be monitored closely [214]. Hydromorphone and fentanyl are the most potent opioids; neither drug should be given to an opioid-naïve patient. Hydromorphone, which is four times as potent as morphine, is available in immediate- and extended-release forms [252]. Fentanyl is the strongest opioid (approximately 80 times the potency of morphine) and is available as a transdermal drug- delivery system (Duragesic; Ionsys), buccal film (Onsolis), tablet (Fentora), nasal spray (Lazanda), sublingual spray (Subsys), sublingual tablet (Abstral), and lozenge (Actiq) [247; 253]. Fen- tanyl preparations have a more rapid onset than other opioids given nonparenterally [223]. Because of its potency, fentanyl must be used with extreme care, as deaths have been associated with its use. Physicians must emphasize to patients and their families the importance of following prescribing information closely, and members of the healthcare team should monitor the use of the drug. Fentanyl, administered subcutaneously, is the recommended choice for patients with advanced chronic kidney disease [214]. The use of methadone to relieve pain has increased substan- tially over the past few years, moving from a second-line or third-line drug to a first-line medication for severe pain in
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MDCA1525
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