Fentanyl is better tolerated in patients with poor renal function since it does not have any active metabolites. It can be administered with a transdermal patch, which is useful in patients who are unable to swallow. However, it may be difficult to titrate doses up when using the patch formulation because pain can escalate quickly at the end of life. Buccal lozenges and intravenous formulations are also available, but these routes may not be optimal for unresponsive patients at home or in nursing home settings. 169,170 Hydromorphone also does not have significant accumulation in renal failure patients. This potent opioid is available in liquid, tablet, and suppository formulations, making it easier for patients and families to administer in both home and nursing home settings. However, frequent administration is required. 169,170 Methadone has emerged as an ideal therapy for some end-of-life patients due to its long half-life and low cost. Its rapid distribution and slow elimination can provide great pain relief in end-of-life patients, but these same pharmacokinetics can produce oversedation easily during the beginning of therapy. In general, it is not ideal to use methadone to treat breakthrough pain, but it can be helpful to use as a longer-acting agent in conjunction with an immediate-release opioid in end-of-life patients with severe pain. 169,170 Oxycodone, commonly used to treat pain in cancer patients, may be difficult for end-of-life patients to use due to its oral administration. In addition, it is primarily eliminated through the kidneys, so patients with severe renal disease may require dose reductions. Patients on oxycodone may require transition to subcutaneous, transdermal, or intravenous opioids to control end-of-life pain. 169,170 Non-opioid medications can also be given to end-of-life pain patients. NSAIDs can help reduce inflammation, though their side effect profile and oral route of administration may diminish their utility at the end of life. Ketorolac can be given parenterally, but its limit of 5 days of acute administration may not be adequate for all patients. Other adjuvant medications can also be used such as antidepressants and anticonvulsants, but they are generally not available in parenteral formulations and take time to reach maximum effectiveness, limiting their use in the end-of-life setting. 169,170 Pain Management Conclusions Acute and chronic pain are common disease states seen by healthcare providers, and pain management can be complex and time-consuming. The pathophysiology of pain is as diverse as each patient’s characterization of their experience, and to further complicate matters, there is a myriad of treatment options available. It is important for providers to thoroughly assess a patient’s pain before developing an individualized, patient-specific treatment plan that often involves the use of multiple treatment modalities.
Pain management treatment regimens require regular reassessment to ensure the benefits of treatment continue to outweigh the risks, and if this balance shifts, providers should ensure treatment regimens are changed, discontinued, or referred to a more appropriate provider as the patient’s condition evolves. Introduction to Addiction The American Society of Addiction Medicine defines addiction as a chronic medical disease that involves complex interactions among brain circuits, the environment, genetics, and a patient’s life experiences. Those suffering from addiction develop compulsions to repeatedly use substances or engage in behaviors despite harmful circumstances. 171 Addiction can have immediate and long-term consequences on the patient, their family, and society as a whole. Addiction can also be costly; addiction to illicit drugs, nicotine, and alcohol costs the United States over $740 billion annually due to healthcare costs, crime, and lost productivity. 172 Addiction is used as a term to describe the compulsion to seek drugs despite negative consequences but is not a diagnosis itself. 172 The Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) characterizes drug use diagnoses as “substance use disorders”, which are subclassified into mild, moderate, or severe conditions. 173 Treatment of this complex condition can be difficult, and measures must be patient-specific and focus on several aspects of the patient’s health, including medical, psychological, and social problems in addition to the drug use itself. Much effort has gone into evaluating effective treatments in an effort to decrease morbidity and mortality. 174 Causes of Addiction The etiology of addiction is not well understood, but research suggests it is a complex and chronic brain disorder. One widely accepted theory involves the activation of the mesolimbic dopaminergic system, known as the brain’s “reward system”. Addictive substances enhance the release of dopamine from neurons in the ventral tegmental area and signal reward or feelings of pleasure. Since dopamine also activates conditioning and memory mechanisms in the brain, the satisfying behaviors are reinforced and continued, and the brain becomes accustomed to this stimulation. The user may feel strong cravings for the substance, especially when surrounded by environmental factors associated with substance use. These may include stress, negative feelings, or other people who normally use with them. 175,176 Over time, individuals can become less able to control their drug use. The brain increases motivation toward desirable behaviors involving drugs and decreases motivation for non-drug rewards that once brought pleasure; the individual’s motivation to take the drug is driven by conditioned responses to signals and by negative emotional situations. This means the addict focuses on immediate reward and the high levels of dopamine released from drugs.
Pain Management in Terminally Ill Patients Pain is one of the most common fears among patients with a terminal illness. A 2016 study showed that over 80% of patients who are terminally ill wish to have a pain-free death. Uncontrolled pain can cause substantial distress in both end-of-life patients and their families or caregivers. 169 When managing severe pain in terminally ill patients, a comprehensive pain assessment should be completed initially, and pain should be reassessed frequently since end-of-life conditions can progress rapidly. Pain should be treated early in order to achieve the best possible outcomes, because it often takes longer to subside in terminally ill patients. An individualized pain management plan should be created for each patient, and pain levels as well as the presence of side effects should be monitored continually. 169 It is common for patients with terminal illnesses to lose their ability to communicate or describe their pain over time. In the last week of life, only 43% of patients are able to communicate 5 days before their death, 28% are able to communicate 3 days before their death, and 13% are able to communicate 1 day before their death. Family members can be asked to describe if they believe the patient is in pain, but research suggests that family assessment frequently underestimates pain, resulting in inadequate pain management. Patients who are unresponsive should be observed for nonverbal signs of discomfort or pain, such as moaning or crying, facial grimacing, shaking or trembling, guarding certain areas of the body, or excessive perspiration. These signs may worsen with movement, such as positioning or turning the patient. Loss of a patient’s ability to communicate at the end of life can take a significant toll on family members and caregivers, and it is critical to ensure appropriate measures are taken to manage pain throughout the process of dying. 161 Pharmacotherapy is a critical component of pain management at the end of life, with opioids being the most commonly used class of analgesics. In addition to their potency, opioids possess mild anxiolytic and sedative properties, which can be beneficial in terminally ill patients. They are also able to be given by multiple routes of administration, which is helpful when patients lose the ability to swallow or become unresponsive. Over 75% of cancer pain patients experience adequate pain relief with opioids, showing their significant effectiveness in treating severe pain. Opioids commonly used at the end of life include morphine, fentanyl, hydromorphone, oxycodone, and methadone. 169,170 Morphine is perhaps the most frequently used opioid in end-of-life pain management. Morphine has active metabolites that can accumulate in patients with inadequate renal clearance, so it should be avoided in those with renal failure. Accumulation can enhance the analgesic potency of morphine, leading to sedation, respiratory depression, worsening nausea, delirium, and neuroexcitability. 169,170
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