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به نام جان پنهان جهان.... Management of Pain at End of Life Dr. Karimpour Definition The World Health Organization (WHO) defines palliative care a n “an approach that improves the quality of life of patients and their families facing the problem. whereas palliative medicine refers to the medical subspecialty focused on providing symptom relief and decision – making support for patients with serious illnesses. History of Palliative Medicne The word palliative comes from the latin word to clothe and refers to the “covering up” of symptoms such as pain. modern palliative medicine grew out of the hospice movement that was started by Dr.Cicely Saunders in 1960 Why is palliative care medicine needed? Patients with serious illnesses have a significant symptom burden, most often involving pain, dyspnea, anxiety, and depression, and their family members report similar concerns. Although the quality of pain control during a life- limiting illness is often a major concern of patients and their families, several surveys have found that they are often dissatisfied with the quality of pain control. INPATIENT PALLIATIVE CARE TEAMS In patient palliative care teams reduce hospital costs. A retrospective study of six hospitals with well established palliative care teams showed a decrease of 1700 () per admission for patients discharged alive and 5000() for patients who died. Palliative care teams become involved with a reduced length of stay in the intensive care unit(ICU) and fewer deaths in the ICU. Inpatient palliative care teams increase patient quality of life and patient and caregiver satisfaction. Palliative care team Teams are interdisciplinary and Include a nurse, physician, social worker, and chaplain as well as other professionals, depending on the need. CANCER Cancer pain syndromes can be grouped in a variety of categories: acute versus chronic, somatic versus neuropathic, and disease versus treatment related11 Acute pain is generally due to invasive procedures, such as diagnostic or surgical interventions, and is not unlike the experience of patients with nonmalignant disease. Examples of treatmentrelated acute pain unique to individuals with cancer are noted in Table 70-1. Chronic pain syndromes often include involvement of bone, soft tissue, the viscera, and the nervous system. Bone metastases are common sources of pain, particularly in patients with breast, lung, or prostate cancers CANCER Lymphedema, occurring in approximately 20% of women who undergo axillary node dissection, is an example of soft tissue pain associated with significant physical and psychological morbidity.12 Visceral pain may arise from involvement of tumor within the liver, intestine, kidney, peritoneum, bladder, or other organs. Neuropathic pains can evolve from numerous causes, may be difficult for patients to describe, and are often complex to treat (see Table 70-2).13–15 Finally, many people with cancer experience syndromes unrelated to the cancer or its treatment, such as osteoarthritis. CANCER Examples of treatmentrelated acute pain unique to individuals with cancer are noted in Table 70-1. Chronic pain syndromes often include involvement of bone, soft tissue, the viscera, and the nervous system. Bone metastases are common sources of pain, particularly in patients with breast, lung, or prostate cancers. Lymphedema, occurring in approximately 20% of women who undergo axillary node dissection, is an example of soft tissue pain associated with significant physical and psychological morbidity.12 Visceral pain may arise from involvement of tumor within the liver, intestine, kidney, peritoneum, bladder, or other organs. Neuropathic pains can evolve from numerous causes, may be difficult for patients to describe, and are often complex to treat (see Table 70-2).13–15 Finally, many people with cancer experience syndromes unrelated to the cancer or its treatment, such as osteoarthritis. ASSESSMENT OF PAIN AT THE END OF LIFE The assessment techniques described in other chapters should be applied to patients with cancer or other lifethreatening illnesses. Intensity, location (or often, multiple locations), quality, temporal nature of the pain, and factors that alter the pain are critical to ascertain. As with all other pain syndromes, a thorough history is followed by a comprehensive physical examination, with particular emphasis on the neurologic evaluation.16 Radiographic, laboratory, and other diagnostic techniques may be indicated, although in caring for those at the end of life, treatment decisions may be made empirically to avoid uncomfortable scans or invasive procedures. ASSESSMENT OF PAIN AT THE END OF LIFE As with all other pain syndromes, a thorough history is followed by a comprehensive physical examination, with particular emphasis on the neurologic evaluation. Radiographic, laboratory, and other diagnostic techniques may be indicated, although in caring for those at the end of life, treatment decisions may be made empirically to avoid uncomfortable scans or invasive procedures. ASSESSMENT OF PAIN AT THE END OF LIFE When patients are unable to verbalize or describe their pain, clinicians can use the furrowed brow as a proxy measure of pain.17 If there is no response to adequate doses of opioids or other analgesics, additional sources of distress (e.g., distended bladder or fecal impaction) should be explored. While the general assessment of pain is universal, several additional dimensions are critical at end of life ASSESSMENT OF PAIN AT THE END OF LIFE . A psychosocial assessment is indicated, directed towards the meaning of the pain as well as the effect of pain on the patient and their caregiver. The findings of this assessment may suggest the need for education, to mediate fears of addiction, for example. The results of this questioning may also prompt referral to social workers, chaplains, or others who are trained to address the existential distress or suffering experienced by the patient or their family. ASSESSMENT OF PAIN AT THE END OF LIFE Pain does not exist in isolation and symptom clusters are common, particularly at end of life. Several instruments have been designed to measure clinically multiple symptoms, including the Edmonton Symptom Assessment Scale (ESAS),20,21 the M.D. Anderson Symptom Inventory (MDASI),22 the Memorial Symptom Assessment Scale (MSAS),23 and others. Another tool, the Distress “Thermometer,” is a vertical visual analog scale designed to look like a thermometer, with 0 meaning “no distress” and 10 (at the top of the thermometer) indicating “extreme distress.” 24 Accompanying the distress scale is a checklist of various physical, psychological, practical, family support, and spiritual/religious concerns. ASSESSMENT OF PAIN AT THE END OF LIFE These are brief, clinically useful tools that quantify the intensity of a variety of symptoms common at end of life (see Table 70-4). The specific needs of people enrolled in hospice are addressed in the Brief Hospice Inventory (BHI). The BHI assesses when managing complex pain syndromes that occur at the end of life. outcomes of hospice patients, including physical and psychological symptoms, patient’s perceptions of hospice care, as well as ratings of their quality of life. ASSESSMENT OF PAIN AT THE END OF LIFE Each statement is measured using an 11-point scale. Benefits of these instruments include the systematic assessment of pain and other symptoms. These data inform the clinician as a treatment plan is developed, particularly when managing complex pain syndromes that occur at the end of life. COMPLEX PAIN SYNDROMES AT END OF LIFE Unfortunately, a small percentage of patients will experience complex syndromes that do not respond to traditional approaches, such as bone pain, intractable neuropathic pain, or malignant bowel obstruction, or will develop severe opioid-induced toxicity. MALIGNANT BONE PAIN Bone pain is often difficult to treat, in that patients may obtain good relief of movement-associated pain from higher-dose opioid therapy, yet will be extremely sedated when they stop moving or placing pressure on the bone. Patients at risk include those with cancers that frequently metastasize to bone, including breast, lung, prostate, or multiple myeloma.5 Table 70-5 lists treatment options. INTRACTABLE NEUROPATHIC PAIN Neuropathies can be difficult to treat. Standard therapies include opioids and adjuvant analgesics, including corticosteroids (Table 70-5).16,27 Additionally, nerve blocks and other interventional techniques can be useful. In more refractory cases intravenvous lidocaine infusions are used to treat intractable pain. Using techniques and protocols originating from pain clinics, intravenous lidocaine 1 to 2 mg/kg is given over 15 to 30 min. If effective, a continuous infusion of 1 to 2 mg/kg/hr is started. The analgesic effects can be as prolonged as weeks of relief. Perioral numbness is an early warning sign of potentialtoxicity. Hepatic dysfunction and significant cardiac conduction abnormalities are relative contraindications to the treatment, viewed in balance with the patient’s goals of care and prognosis. MALIGNANT INTESTINAL OBSTRUCTION Bowel obstruction is common in progressive gynecologic and colorectal malignancies. The majority of patients with bowel obstruction will die within 6 months. Palliation can include surgery in selected cases, or, more commonly, intravenous or subcutaneous octreotide, nasogastric tube suction, and venting gastrostomy, in addition to analgesics and antiemetics.30 Table 70-5 lists specific treatment options. OPIOID NEUROTOXICITY The neuroexcitatory effects of opioids include myoclonus, hyperalgesia, delirium, and grand mal seizures. These toxicities have been reported in association with morphine, hydromorphone, hydrocodone, fentanyl, methadone, and oxycodone.31,32 The 3-glucuronide metabolites are implicated as contributing to these neuroexcitatory effects.33 Both morphine-3-glucuronide (M3G) and hydromorphone-3-glucuronide (H3G) are believed to produce myoclonus and seizures. Renal failure appears to be a significant, but not absolute, risk factor, as patients are unable to clear the metabolite. OPIOID NEUROTOXICITY Case reports suggest that H3G plasma levels are greatly increased in the presence of renal failure, with the ratio of H3G to the parent compound four times higher thanthe ratio seen in patients with normal renal function.35 The treatment of mild myoclonus generally includes switching to another opioid, lowering the dose of the opioid, and adding a benzodiazepine. Clonazepam 0.5 mgorally twice daily with upward titration may be effective. If the patient is unable to swallow, midazolam or lorazepam may be used. Hyperalgesia frequently is misdiagnosed and the first response by well-meaning clinician often is to increase the opioid dose. OPIOID NEUROTOXICITY This generally results in greater pain, with potential progression to delirium and possibly seizures. When these more severe neurotoxicities occur, the opioid dose should be reduced by at least 50%. Some advocate stopping the opioid altogether, since the half-life of these metabolites is long and the patient is unlikely to experience the abstinence syndrome. Naloxone appears to be ineffective in reversing this toxicity. In select cases, spinal delivery of analgesics can be effective in relieving pain and reducing systemic opioid exposure. Should seizures occur, first- and secondline therapies include phenytoin and benzodiazepines, such as diazepam or lorazepam. OPIOID NEUROTOXICITY In some cases the seizures will progress in frequency and intensity, advancing to status epilepticus.38 Refractory status epilepticus treatment may require midazolam, barbiturates, and propofol.39 l Midazolam is particularly useful in palliative care due to its rapid onset and short duration, as well as its ability to be given subcutaneously, intravenously, orally, buccally, sublingually, or rectally. Furthermore, its only known drug incompatibility is with corticosteroids, particularly betamethasone, dexamethasone, and methylprednisolone.39 l The standard dose of phenobarbital in the management of seizures is 20 mg/kg intravenous infusion, with a maximum rate of 50 to 100 mg/min. The recommended dose of propofol to treat refractory status epilepticus is 1 to 2 mg/kg via intravenous injection over 5 min and repeated if necessary. A maintenance intravenous infusion of 2 to 10 mg/kg/hr is then started, using the lowest dose needed to suppress seizure activity. OTHER SYMPTOMS COMMON AT END OF LIFE Dyspnea, anxiety, depression, and other symptoms are common in the face of advanced illness. Palliation of these symptoms, which are frequently linked with pain, can result in improved pain control and enhanced quality of life. DYSPNEA Dyspnea, or air hunger, can occur as a result of a variety of illnesses, including cancer, congestive heart failure, or pulmonary diseases. Opioids are the first drug of choice, often in small doses that do not cause sedation. Shortacting anxiolytics are indicated in the face of severe anxiety. Simple measures such as bedside fans can provide additional comfort. ANXIETY Anxiety is highly correlated with unrelieved pain.41 Additionally, many medications commonly used in palliative care, such as corticosteroids, neuroleptics (including metoclopramide), bronchodilators, antihistamines, digitalis, and occasionally benzodiazepines (which can cause a paradoxical reaction in elderly patients), can result inmotor restlessness and agitation. Abrupt withdrawal from alcohol, opioids, benzodiazepines, and nicotine also produce agitation. Hypoxia, pulmonary embolus, sepsis, hypoglycemia, thyroid abnormalities, and heart failure are associated with anxiety, as are certain tumors, including pheochromocytomas, and some pancreatic cancers. Primaryor metastatic lung cancers and chronic cardiopulmonary conditions can lead to dyspnea, which can also produce anxiety. ANXIETY Pharmacologic treatment of anxiety usually consists of benzodiazepines, particularly lorazepam as it has a short duration of action and produces fewer adverse effects. A typical initial dosage is 0.5 to 2 mg orally 3 or 4 times daily. Lorazepam can be placed sublingually, which is useful when patients have difficulty swallowing, or given parenterally as a bolus or infusion. Haloperidol is frequently used for short-term management of severe anxiety and as an antipsychotic, with initial dosage starting at 0.5 to 1 mg orally twice daily.41 Frank discussion of patients’ fears in a supportive environment, along with the use of relaxation strategies, such as audiotapes, breathing exercises, and guided imagery, may alleviate anxiety. DEPRESSION Depression is often poorly recognized in people at end of life.43 Diagnosis may be difficult in advanced disease, as the usual physical symptoms of depression (fatigue, anorexia, and sleep disturbance) can result from the disease itself or its treatment. Psychological symptoms suggestive of depression in the patient with life-threatening illness include loss of selfworth, unremitting sadness and hopelessness, and suicidal ideation. There is evidence that a simple screening question “Are you depressed?” or “Are you sad?” is the most valid measure of a patient’s depression.44 Supportive psychotherapy may be of benefit, although limited life span may be a barrier. DEPRESSION Antidepressant medications, such as serotoninspecific reuptake inhibitors (SSRIs), such as citalopram, fluoxetine, paroxetine, and sertraline, are usually well tolerated. However, the 2 to 4 weeks required for the drug to take effect is often too long for patients with advanced disease and a very short life span. Newer, “atypical antidepressants” (bupropion, mirtazepine, and venlafaxine) have a relatively rapid onset of action and few reported side effects. However, for patients with a very limited life span, stimulants such as methylphenidate and pemoline provide rapid relief, usually within hours to days. CONCLUSION Pain, dyspnea, anxiety, and depression are serious symptoms experienced by people with life-threatening illnesses. All health-care professionals are responsible for care of the dying, and, therefore, must be aware of the most common syndromes occurring in this population, able to conduct specific assessment techniques, and knowledgeable about the therapies used to treat these symptoms. Resources, such as palliative care services and hospices, can assist physicians as they provide care to these patients and their families. از مرگ دگرچرا هراسم؟ کان راه به توست می شناسم....