Indeed many people consider the experience of severe pain to be worse than death, which underscores the importance of a thorough clinical understanding this issue. 38 Managing pain and other symptoms at the end of life is just one component of a wider effort to relieve suffering and help a patient cope with the emotional and psychological aspects of dying. Nonetheless, a failure to manage pain and other symptoms may make it impossible for the patient to attend to these important dimensions. Uncontrolled pain can push all other priorities aside and sap a person’s energy and motivation to focus on potentially positive goals or meaningful experiences. A patient’s perception that his or her pain cannot be controlled may also contribute to a broader feeling that he or she has lost control over their lives in general, which can precipitate a downward spiral of depression and/or hopelessness. Effective pain control, on the other hand, not only directly reduces suffering but may allow a patient the energy and positive attitude needed to engage with the emotional and psychological aspects of dying. Assessing Pain at the End of Life The end of life is often characterized by a reduced level of consciousness or complete lack of consciousness. This can make assessments of pain very challenging. If a patient is not alert enough to communicate, then nonverbal signs or cues must be used to determine if the patient is experiencing pain and to what degree an analgesic approach is effective. In general, even ambiguous signs of discomfort should usually be treated, although caution must be exercised in interpreting such signs. 39 Patients who are actively dying may groan or grunt in ways that suggest they are in pain, although such sounds may, in fact, be the normal expressions attendant to the last moments or hours of life. 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 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 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, 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. BEFORE MOVING ONTO THE NEXT SECTION, PLEASE COMPLETE CASE STUDY 4 ON THE NEXT PAGE. Non-steroidal Anti-inflammatory (NSAID) Analgesics and Acetaminophen NSAIDs or acetaminophen may be useful in the treatment of pain conditions mediated by inflammation, including those caused by cancer, such as bone metastases. 41 NSAIDs typically cause less nausea than opioids, though this is most true with low doses. NSAIDS also do not cause constipation, sedation, or adverse effects on mental functioning. NSAIDs may, therefore, be useful for the control of moderate to severe pain, usually as an adjunct to opioid analgesic therapy. 50 The addition of NSAIDs to an opioid may allow a reduction in the opioid dose, although such combinations must be used with care. Typically, the non-opioid co-analgesic agent, such as acetaminophen or an NSAID, has a ceiling dose above which efficacy will plateau as risk for adverse effects increases. Thus, combining these products, either as separately- administered agents or in combination products, are typically used for patients who are not expected to need substantial dose escalations. 19 Using a combination product when dose escalation is required risks increasing adverse effects from the non-opioid co-analgesic, even if an increase of the opioid dose is appropriate.
11
Powered by FlippingBook