Signs of discomfort that are accompanied by more rapid breathing or heart rate should be taken more seriously. Likewise, if physical stimulation of the patient (i.e., during bathing) causes signs of discomfort, increased analgesia may be warranted. Prolonged Opioids Opioid formulations are available in such variety in the US that, typically, a pain regimen can be tailored to each patient. 40 Because there is great variability in how individual patients respond to particular opioid agents, no specific agent is superior to another as first-line therapy. Although morphine was previously considered the ‘‘gold standard,’’ it is now recognized that the most appropriate agent is the opioid that works for an individual patient. 41 Morphine and other opioids are generally available in a wide range of formulations and routes of administration, including oral, transmucosal, transdermal, parenteral, and rectal delivery. Both rectal and transdermal routes can be especially valuable at the end of life when the oral route is precluded because of reduced or absent consciousness, difficulty swallowing, or to reduce the chances of nausea and vomiting. 42 When selecting an opioid, clinicians should also consider cost, since expensive agents can place undue burden on patients and families. Some opioids may not be appropriate in the end- of-life setting. For example, meperidine is not recommended in cancer pain management due to the neurotoxic effects of its metabolites. 43 In addition, mixed agonist-antagonist opioid analgesics, including butorphanol, nalbuphine, and pentazocine, are not recommended in cancer pain management because they are more likely to cause psychotomimetic effects and they can precipitate the abstinence syndrome if given to a patient who is physically dependent on a pure opioid agonist. 43 Opioid-related side effects must be considered in advance of treatment and steps must be taken to minimize these effects to the extent possible, since adverse effects contribute significantly to analgesic nonadherence. This is particularly true for constipation and sedation. Tolerance rarely develops to constipation and therefore it must be prevented and, if unsuccessful, treated aggressively. A prophylactic bowel regimen that includes a laxative and stool softener, such as senna and docusate, should be used, although a recent study suggested that senna alone was just as effective. 44 Bulking agents, such as psyllium, are ineffective and may exacerbate gastrointestinal distress unless the patient can drink significant amounts of fluids. Methylnaltrexone, an opioid antagonist that works on receptors in the GI system and is given subcutaneously, can be used as a rescue when constipation is clearly related to opioid therapy. 45 Two, more recently-approved opioid antagonists are naldemedine and naloxegol. Sedation is often attributed to opioid therapy given at the end of life, although many other drugs used at this time may be sedating, including benzodiazepines,
rapid breathing (> 20/min.) may be uncomfortable because of muscle fatigue and it may therefore be reasonable, even in the absence of other evidence of discomfort, to titrate a pain medication with a target respiratory rate of 15 to 20/minute. 39 antiemetics, and other agents. Tolerance to opioid- induced sedation may develop within a few days of regular use; however, in some cases this may persist and opioid rotation may be warranted. A psychostimulant, such as methylphenidate or dextroamphetamine, might be added to offset sedative effects, typically starting at a dose of 5 to 10 mg once or twice daily. One study found that with proper timing, the administration of methylphenidate did not disrupt sleep. 46 Other drugs to be considered for similar indications are modafinil (Provigil) and armodafinil (Nuvigil). Nausea and vomiting are relatively common in opioid- naive individuals. Around-the-clock antiemetic therapy instituted at the beginning of opioid therapy may prevent this adverse effect. 41 The antiemetic can be weaned in most cases after 2 to 3 days. The itching that can occur early in the course of opioid treatment may be at least partially alleviated with antihistamines. Opioid rotation to a more synthetic agent or an agent with a different route of administration, such as oxymorphone or transdermal fentanyl has also been reported to be helpful. The potential adverse effect of respiratory depression may lead to clinician under-prescribing of opioids or the reluctance by patients to take the medication. 41 Despite this fear, studies have revealed no correlation between opioid dose, timing of opioid administration, and time of death. 47,48 Even when a medication, such as an opioid, that is intended to relieve pain and symptoms but does pose a possible risk of hastening death, it is considered ethical for health care providers to prescribe and to administer the medication following the rule of “double effect.” 49 This rule distinguishes between practices that are intended to relieve pain but which may have an unintended effect of hastening death vs. practices that are actually intended to hasten death. When an action has both potentially good and bad effects, it is considered ethically acceptable to pursue the action if four conditions are satisfied: 49 1. The action itself (e.g., administering a pain medication) is not morally wrong. 2. The action is undertaken with the sole intention of bringing about the good effect. 3. The action does not bring about the good effect by means of the bad effect (e.g., in the case of EOL pain medications, such medications do not achieve their effect by ending life). 4. The reason for undertaking the action is clear and urgent.
Book Code: CA23CME
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