Meira Epplein, PhD
https://medicine.duke.edu/faculty/meira-epplein-phd
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Dyspnoea is a term we use for a symptom that patients often describe as breathlessness medicine knowledge order trileptal 300 mg without a prescription. Dyspnoea prevalence, pattern, and trajectory Dyspnoea is common among patients with advanced cancers and non-cancer life-limiting illnesses. The prevalence of dyspnoea varies with the site of primary cancers and the stage of illness. Similar to the pain model, it is postulated that dyspnoea consists of multiple dimensions, including the independent component of sensory dimension (sensory intensity and sensory quality), immediate affective stage which trigger immediate behaviour, and a stage of cognitive evaluative and emotional response which affects long-term behaviour (Lansing et al. Against the traditional neurochemical and neuromuscular model, a neuromatrix-gated model has been proposed to unify multiple factors by recognizing different inputs from afferents at receptor levels and inputs from different areas of the brain (Williams, 2011). Patients with non-cancer diagnoses had significantly higher levels of breathlessness at all three time points, while cancer patients had less breathlessness initially but increased significantly at day 10 and day 3 before death. In another cohort of over 10,000 cancer patients, the trajectories of performance status and symptom scores during the last 6 months of life were evaluated (Seow et al. Breathlessness increased in severity over time, particularly in the month before death. Qualities of dyspnoea and neurophysiology There are at least three separate qualities of dyspnoea: air hunger or unsatisfied inspiration; work or effort; and tightness (Lansing et al. This classification depends on different perceptual qualities with distinct afferent sources: 1. Air hunger or unsatisfied inspiration: this is the conscious perception of the urge to breathe. This sense of air hunger can be experimentally induced by hypercapnia, hypoxia, exercise, or acidosis, all leading to increase in respiratory drive. The signal comes from the motor drive of the respiratory centres in the brainstem, and is conveyed to the cerebral cortex as corollary discharge. When this is not matched by an adequate ventilatory response by feedback from afferent receptors throughout the respiratory system, individuals perceive air hunger or unsatisfied inspiration. Afferent information about the pulmonary ventilation achieved from mechanoreceptors in the lungs, airways, and chest wall can relieve or inhibit air hunger or unsatisfied inspiration. The sense of work or effort can be produced experimentally by external resistive or elastic load, volitional hyperpnoea, or by weakening of the respiratory muscles. The sensation of tightness arises from pulmonary afferents through the stimulation of airway receptors. The most consistent and the strongest area of activation is in the right anterior insula (Lansing et al. Other activations can be seen in the left anterior insula, anterior cingulate, supplementary motor area, prefrontal cortex, cerebellum, and amygdala (Parshall et al. Dyspnoea is associated with activation of cortico-limbic structures, which overlap with that observed the impact of dyspnoea Breathlessness correlates with survival and is a predictor of poor prognosis in cancer. In a systematic review of the value of symptom assessment to predict survival in people with advanced cancer, dyspnoea was evaluated in 35 studies involving 9155 patients (out of 44 studies included).
Radiation fibrosis syndrome: neuromuscular and musculoskeletal complications in cancer survivors treatment centers in mn buy cheap trileptal 150 mg online. Video fluoroscopic analysis of the effects of three commonly-prescribed off-the-shelf orthoses on vertebral motion. A systematic review of conservative treatments for acute neck pain not due to whiplash. Validation of World Health Organization Guidelines for cancer pain relief: a 10-year prospective study. Scrambler therapy may relieve chronic neuropathic pain more effectively than guideline-based drug management: results of a pilot, randomized, controlled trial. Effects of local heat and cold treatment of surface and articular temperature of arthritic knees. Philadelphia panel evidence-based clinical practice guidelines on selected rehabilitation interventions for knee pain. Philadelphia panel evidence-based clinical practice guidelines on selected rehabilitation interventions for low back pain. The causes, presentation, and impact of pain may be highly complex in some patients, and effective management may require the expertise of multiple specialties, including neurology, neurosurgery, anaesthesiology, and rehabilitation medicine (Foley, 1975, 1985; Breitbart, 1990b). Psychiatric and psychological interventions are integral to the comprehensive treatment of pain and distress in these populations (Breitbart, 1989, 1990b; Massie and Holland, 1987). The incidence of pain may be as high as 88%, and 69% of patients may experience moderate to severe pain-related impairment in activities of daily living (Frich and Borgbjerg, 2000). More than 50% required treatment for pain, including chest pain in 22%, headache in 13%, oral cavity pain in 11%, abdominal pain in 9%, and peripheral neuropathy in 6%. The scope of the problem Approximately 70% of cancer patients experience severe pain at some time in the course of their illness (Foley, 1985) and nearly 75% of those with advanced cancer have chronic pain (Fitzgibbon, 2001). Overall, approximately 50% of terminally ill patients are in moderate to severe pain (Weiss et al. This phenomenon presumably has multiple causes, one of which is the complex presentation of pain in populations with advanced illness. In those with cancer, this complexity is partly determined by the common experience of symptoms other than pain, one or more of which may contribute to symptom distress. In one survey, cancer patients had an average of three additional troubling physical symptoms (Grond et al.
Sometimes treatment zinc poisoning buy trileptal 600 mg, combination of agents from different classes is efficacious when a single agent is ineffective. Other drug therapies Cromones and thalidomide are anti-inflammatory agents that have been reported to be useful in pruritus associated with several different types of chronic or malignant disease. Disodium chromoglycate improves the flushing and pruritus of systemic mast cell disease (Soter et al. Thalidomide has been found to relieve the intractable pruritus and development of skin lesions in prurigo nodularis (Winkelmann et al. More recently, thalidomide (100 mg/day) was found to produce significant relief of uraemic pruritus (Silva et al. This drug is used primarily in the treatment of leprosy reactions and graft-versus-host disease. Because of its neuropathic and teratogenic side effects, thalidomide is not routinely available for prescription. However, selected patients who require only a limited course of therapy and can be monitored regularly may be candidates for thalidomide when an alternative medication is sought. Many drugs have effects on the peripheral or central nervous system, and some of these agents have been found to be very useful in the treatment of itching from many causes. Anaesthetic agents administered by the intradermal, intravenous, or intra-arterial routes have effects similar to topical anaesthetics in blocking sensory input and transmission, including the sensation of pruritus. Parenteral lignocaine (200 mg in 100 mL saline by an intra-arterial line) alleviates refractory pruritus in hepatic cholestasis and chronic renal failure (Tapia et al. Hypotension, cardiovascular effects, seizures, and psychosis are possible side effects. Gabapentin and the newer analogue, pregabalin are anticonvulsant drugs with analgesic activity but with no appreciable anti-inflammatory activities. These novel agents have recently been shown to bind to the alpha 2- delta-1 subunit of the voltage-dependent calcium channel and mediate analgesic properties in the brain and spinal cord levels. Both agents have activity in neuropathic pain, and recent clinical evidence indicates effectiveness in pruritus due to uraemic states as well as other types of primary and secondary pruritus, including pruritus following burn injury. Sequestrants such as cholestyramine or charcoal administered orally or heparin administered by intravenous infusion have been reported to be helpful in the treatment of obstructive biliary pruritus (Fransway and Winkelmann, 1988). Cholestyramine was also observed to improve itching in polycythaemia vera and uraemia. These treatments may be useful as adjuvant or alternative therapies during the management of chronic pruritus due to these diseases. Pertinent references reporting the benefit of specific therapies are cited for each modality. For example, several medications and physical modalities have been found to relieve the pruritus of chronic renal failure. Interferon- and rifampicin have been found to be effective for polycythemia vera and malignant cholestatic pruritus, respectively (Price et al.
Neurosurgical interventions for intractable pain: intracerebroventricular opioid and neuro-destructive interventions Catheter techniques are rarely used for opioid administration directly into the cerebral ventricles (Raffa and Pergolizzi medicine 93 5298 purchase trileptal 600mg mastercard, 2012). Relative contraindications include posterior vertebral defects, epidural tumour spread, and cervical fractures. The overall complication rate for these procedures is low, but cement extrusion into the spinal canal can result in neural compromise, and cement venous embolism can cause pulmonary embolism (Burton et al. In recent years, with increasing use of systemic and spinal analgesics, there has been a reduction in use of destructive neurosurgical procedures for control of intractable pain. Nonetheless, these techniques are potentially valuable in selected pain syndromes (Raslan and Burchiel, 2010). These procedures most commonly target the spinal cord, but may target the brainstem or brain. Percutaneous, image-guided ablation techniques potentially limit the need for open surgical interventions. Spinothalamic cordotomy, the most common, is best used for intractable unilateral somatic pain in the lower body (or at least below the level of the neck) (Raslan et al. Rarely, midline myelotomy (for midline visceral pain) and dorsal root entry zone lesioning (for localized neuropathic pain such as brachial plexopathy) are considered (Romanelli et al. A trial using temporary leads can help determine patient response prior to permanent placement. Miscellaneous techniques for pain control Vertebroplasty and kyphoplasty Vertebral compression fractures are an important cause of pain and morbidity in patients with serious illnesses and can be caused by metastatic cancer, multiple myeloma, or bone loss after radiotherapy, hormonal treatment, steroids, and poor overall medical status (Aghayev et al. Osteoporotic vertebral compression fractures not only are painful, but increase mortality (Bliuc et al. Percutaneous vertebroplasty and kyphoplasty are similar minimally invasive procedures, in which a fractured vertebra is stabilized by injection of polymethylmethacrylate bone cement into the vertebral body via large-bore needles (Burton et al. In vertebroplasty, bone cement is injected through needles into the interstices of the vertebral body marrow space. Kyphoplasty includes inflation of a high-pressure balloon in the vertebral body to create a cavity, which is subsequently filled with bone cement. The balloon expansion may partially restore vertebral height, but the degree of height restoration may be modest and is of unclear significance. A randomized, controlled trial comparing kyphoplasty with non-interventional, conservative management strongly favoured kyphoplasty in terms of pain, disability, quality of life, and decreased analgesic use (Berenson et al. Rapid pain relief from percutaneous vertebroplasty or kyphoplasty may improve patient tolerance of needed antitumor therapies, such as positioning for radiation therapy (Aghayev et al. Bone scintigraphy is less useful because it will identify increased activity at a fracture site for up to 2 years, long after the fracture may have spontaneously stabilized. Absolute contraindications for vertebral augmentation are spinal cord compression with clinical myelopathy, overt spinal instability Palliative sedation: management of intractable pain when all else fails Despite advances in palliative care, a few patients still experience distressing end-of-life symptoms, including pain or delirium (Maltoni et al. Palliative sedation is a medical intervention, clearly different than euthanasia, and accepted guidelines for proper use have been proposed (Cherny and Radbruch, 2009).
The potential for additive side effects and serious toxicity from drug combinations must be recognized treatment receding gums order trileptal 150 mg amex. The sedative effect of an opioid may add to that produced by numerous other centrally-acting drugs, such as anxiolytics, neuroleptics, and antidepressants (Bennett 2011). Likewise, drugs with anticholinergic effects probably worsen the constipatory effects of opioids. As noted previously, a severe adverse reaction, including excitation, hyperpyrexia, convulsions, and death, has been reported after the administration of pethidine (meperidine) to patients treated with a monoamine oxidase inhibitor (Browne and Linter 1987). Gastrointestinal side effects the gastrointestinal adverse effects of opioids are common. Constipation All opioids cause constipation and tolerance to this effect is not observed over time. There are some data to indicate that the severity is less severe with fentanyl and, possibly, methadone (Pappagallo, 2001; Staats et al. The likelihood of opioid-induced constipation is so great that laxative medications should be prescribed prophylactically to most patients (Ahmedzai and Boland, 2010). There is some evidence from randomized controlled trials, supported by consensus, that the oral laxatives lactulose, polyethylene gycol/electrolyte solutions and senna are probably of similar efficacy in people with opioid-induced constipation and that the polyethylene glycol/electrolyte solutions may have a better adverse effect profile than the other oral laxatives (Ahmedzai and Boland, 2010). It antagonizes only peripherally located opioid receptors while sparing centrally mediated analgesic effects of opioid pain medications. There is evidence of very predictable effectiveness after administration by either oral or parenteral routes of administration with most patients achieving defecation within 90 minutes of administration (Ahmedzai and Boland 2010; Candy et al. In many countries, an oral prolonged-release preparation containing oxycodone and naloxone in a ratio of 2 to 1, is available. Efficacy in preventing and or managing opioid related constipation is based on the fact that oral naloxone binds to gut opioid receptors with a greater affinity than oxycodone, however, naloxone that undergoes metabolism in the liver where it is rendered inactive, while oxycodone passes through the liver unchanged. A randomized controlled trial demonstrated that prolonged release oxycodone and naloxone combination provides superior bowel function in cancer pain patients, compared with prolonged release oxycodone alone, without compromising analgesic efficacy or safety (Ahmedzai et al. Switching route of systemic administration Limited data indicate that some adverse side effects among patients receiving oral morphine can be relieved by switching the route of admission to the subcutaneous route. In one small study this phenomenon was reported for nausea and vomiting (McDonald et al. Initial management of the patient receiving opioids who presents with adverse effects Among patients receiving opioid analgesic therapy there are two key steps in the initial management of adverse effects. Firstly, the clinician must distinguish morphine adverse effects from co-morbidity or drug interactions. This step requires careful evaluation of the patient for factors outlined in Table 9.
Of the 65 male and female respondents treatment meaning buy cheap trileptal 150mg on-line, most respondents (86%) felt it was important to be offered the opportunity to discuss changes to sexuality with trained professionals and half (47%) of the respondents felt sexuality was very important for psychological well-being. While the study did not explore the rate of discussions patients had with their health-care professionals, it was interesting to note that 60% of the patients in this study did not feel less attractive than prior to their diagnosis; however, only 30% respondents felt satisfied with their sexual activity compared to 67% feeling satisfied with their sexual activity prior to the diagnosis. Whilst the reasons for these findings were not explicated in the study, one could assume that if people facing these issues were provided with an opportunity to explore the challenges, and receive practical and evidence-based solutions, then satisfaction rates may have increased. An Australian study has shed light on the intimate and sexual disruptions experienced by carers who are partners of people with cancer (Gilbert et al. When Gilbert and colleagues interviewed 20 participants who were partners across a range of cancer types, stages, and age groups, they found that all partners reported a decrease in levels of sexual expression and frequency of intercourse. The authors highlighted the experience of some partners who were unable to negotiate other forms of intimacy when penetration was no longer an option. This study also highlighted the importance of couple communication, where poorer communication decreased both relationship and sexual satisfaction. When couples found it difficult to communicate about their own sexual needs and concerns, a cycle increasing distance occurred between the partners causing isolation, fear, and distress. Due to the lack of research into the impact of sexuality and intimacy on the partner in non-cancer-related areas of palliative care, one can assume that these findings are transferable to other life-limiting diseases. Health professionals can play an important role in assisting both the patient and their partner to communicate about the impact of advanced disease on intimacy and sexuality (Cort et al. These authors suggest social workers are well equipped to conduct discussions and take on patient-centred roles within teams. Other authors suggest that that as long as the communication is patient-centred, well documented, and that the patient feels well supported with information and practical strategies, then the type of health professional providing this level of communication is irrelevant (Hordern and Street, 2007a; Woodhouse and Baldwin, 2008; Hawkins et al. Health professionals do not require specialist training in sexuality to achieve patient-centred outcomes and patients want links to their regular team rather than to a separate sexual counsellor (Cort et al. This was done through in-depth interviews with 32 health professionals representing a multidisciplinary team, a critical review of the literature, and a contextual analysis of 33 national and international cancer and palliative care clinical practice guidelines. The majority of health professionals did not see their patients as sexual beings, avoiding the topic, feeling vulnerable to the reactions of patients and colleagues, and rarely taking the risk of venturing into such a taboo topic with patients in their care. The same researchers also interviewed 50 patients across a range of ages, cancer types, and stages (who were increasingly armed with information downloaded from the Internet). The patients wanted information and support about how to live with and manage the side effects of treatment that was impacting their sexual and intimate worlds, how others cope, and the choices they could make to regain sexual confidence until the end of life. Hordern and Street suggested that these mismatched expectations between patient and health professionals could be overcome by health professionals reflecting upon and recognizing the personal and professional influences that shape their beliefs about patient sexuality and checking their assumptions with the patients in their care (Hordern and Street, 2007b, 2007d). With the dearth of research into the area of communicating about patient sexuality in the non-cancer palliative care context, one can assume that the key barriers and challenges in the communication process are transferable to other advanced and terminal disease states. Normal ageing processes for women Irrespective of health and disease status, men and women experience changes to sexual function as a result of natural ageing processes. For example, in natural menopause the vaginal tissue becomes drier, thinner, and more fragile.
Surgery is also performed as a definitive treatment medications hydroxyzine trileptal 600mg amex, to prevent recurrence, as in aspergilloma (Sakr and Dutau, 2010). When the patient is unfit for surgery, percutaneous treatment such as radiofrequency ablation of lung cancer has been used to control severe haemoptysis (Baisi et al. Do the trajectories of dyspnea differ in prevalence and intensity by diagnosis at the end of life Massive hemoptysis: an update on the role of bronchoscopy in diagnosis and management. A 44-year-old man with hemoptysis: a review of pertinent imaging studies and radiographic interventions. Management of fatal haemoptysis If a patient is at risk of massive haemoptysis, it is essential to establish an action plan in anticipation (see Chapter 8. The patient and family need to be informed, psychologically prepared, with possible treatment options discussed. If a massive life-threatening haemoptysis occurs, sedation to relieve the distress should be given as soon as possible. Zhu and Cynthia Wu Anaemia and cytopenias Introduction to anaemia and cytopenias the illnesses, malignant or benign, that bring patients to a palliative care setting are often complicated by haematological problems such as anaemia, bone marrow failure, disseminated intravascular coagulopathy, and thrombosis. Supportive therapy for these problems can provide gratifying relief of symptoms and improvement in overall quality of life. This chapter emphasizes a practical approach to assessment and therapy intended to maximize quality of life. These cytokines stimulate the uptake into and storage of iron in macrophages and monocytes while also preventing the export of iron out of these cells. This results in a paradoxical situation of iron-deficient erythropoiesis occurring in a marrow replete with iron. Simultaneously, the cytokines also suppress the ability of the kidneys to produce erythropoietin, enhance red blood cell membrane damage, and prevent the differentiation and proliferation of red cell progenitors in the marrow. Together, erythropoiesis is reduced resulting in anaemia (Weiss and Goodnough, 2005). Anaemia Anaemia is present in 77% of men and 68% of women receiving palliative care (Dunn et al. Typical symptoms associated with a sudden drop in haemoglobin as seen with acute blood loss include tachycardia, orthostatic hypotension, and dyspnoea.
Changes from baseline in the general subscale of the Multidimensional Fatigue Symptom Inventory-Short Form were 14 medicine x 2016 generic trileptal 300mg amex. Greater benefit was reported in patients receiving active cancer treatment vs those who had completed treatment. In another study by de Oliveira Campos and colleagues, patients with progressive fatigue after their first cycle of chemotherapy were randomized to receive either Paullinia cupana (guarana) 50 mg by mouth twice daily (32 patients) or placebo (43 patients) for 21 days (de Oliveira Campos, 2011). After a 7-day washout period, patients Conclusion Fatigue in cancer patients is now accepted as a symptom that should be studied in its own right. Unfortunately, few studies have addressed fatigue in palliative cancer populations. Consequently, most of the insight into the complexity of fatigue must be based upon extrapolation from studies performed with patients earlier in the disease trajectory. To improve treatment, we must gain a better understanding of the many aspects of fatigue. Thus, identifying the pathophysiological mechanisms that cause fatigue is important. Assessment and staging tools that are valid and reliable are needed to assist in clinical practice and research. Clinical syndromes of fatigue (cognitive, affective, and physical) also must be better characterized. Effects of methylphenidate on fatigue and depression: a randomized, double-blind, placebo-controlled trial. Psychostimulants for the management of cancer-related fatigue: a systematic review and meta-analysis. Acupuncture for cancer-related fatigue in patients with breast cancer: a pragmatic randomized controlled trial. Physical exercise for cancer patients with advanced disease: a randomized controlled trial. The potential of agents such as eicosapentaenoic acid, thalidomide, and anabolic steroids must be explored in studies in which fatigue is a primary endpoint. Finally, the role of psychostimulants should be further researched, and the importance of counselling, rest, and exercise in cancer patients receiving palliative care should be clarified. Wisconsin Ginseng (Panax quinquefolius) to improve cancer-related fatigue: a randomized, double-blind trial, N07C2. Sham Introduction to dyspnoea and other respiratory symptoms in palliative care A breath is a vital sign of a living creature.
Arokkh, 33 years: Clinicians are challenged in these circumstances to find novel approaches to manage the lesions. Proceedings of the National Academy of Sciences of the United States of America, 96, 76757679. Corticosteroids for the resolution of malignant bowel obstruction in advanced gynaecological and gastrointestinal cancer.
Peratur, 51 years: An acidic extracellular microenvironment is highly important for an osteoclast to function properly as it is involved in the predominant mechanism through which osteoclasts degrade the base mineral hydroxyapatite. Anticonvulsants have Adapting treatment to the individual: by the child this principle promotes individualized treatment according to the assessed need of the child. Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomized controlled phase 2 trial.
Gunnar, 53 years: For the specific cohort which requires sedation for intractable pain, recommended therapeutic modalities include opioids, benzodiazepines, neuroleptic, and anaesthetic agents such as propofol (Anghelescu et al. Pharmacotherapy: trainees should have an understanding of the pharmacology and toxicity of non-opioid and opioid medications commonly used in the management of cancer pain. Whole brain radiotherapy for the treatment of newly diagnosed multiple brain metastases.
Ramon, 65 years: The syndrome typically presents as an exacerbation of bone pain or urinary retention; spinal cord compression and sudden death have been reported (Thompson et al. Finally, a reluctance to use high-dose systemic opioid therapy may be justified by concerns related to facilitation of pain transmission (or opioid-induced hyperalgesia) (Ossipov et al. In patients who have been previously treated it is an important symptom of potential recurrence (Portenoy et al.
Kayor, 43 years: The cutaneous vasculature is innervated mainly by adrenergic vasoconstrictor nerve fibres. These two strategies were compared in a randomized, double-blind trial involving 287 arthritis patients who received either diclofenac plus omeprazole, or celecoxib, 200 mg twice daily, for 6 months more effective than placebo for cancer-related pain. The clinician may need to think laterally when considering a neuropathic pain diagnosis in children, for example, the child with unstable kyphoscoliosis and vertebral instability compromising the spinal cord and nerve roots, or the population of infants and children with neurometabolic conditions and white matter anomalies that may cause lesions or disordered processes within the nervous system.
Osmund, 28 years: Oncologist-based palliative care In this model, the oncologist assumes the role of coordinating care and providing both anti-cancer and palliative care services, thus seeing the patient through from diagnosis until death (Cherny, 2003). Persistent suicidal ideation is relatively infrequent, however, and is limited to those who are significantly depressed. Non-pharmacological measures In pruritus of cholestasis the value of topical emollients and environmental measures to cool and lessen sweating is unclear.
Marik, 27 years: In kyphoplasty, a balloon is first inserted through the pedicle into the vertebral body and then inflated. These include suggestions such as avoiding foods that are likely to impair gastric emptying, the use of antacids for intermittent exacerbations, and intermittent prokinetic therapy to promote gastric emptying with either metoclopramide or domperidone, barrier therapy with sucralfate or inhibiting reflux with baclofen (Armstrong and Sifrim, 2010) (see Boxes 10. Although biopsy within a region of raised venous pressure raises concerns about the risk of haemorrhage, in practice bronchoscopy, mediastinoscopy or lymph node biopsy are performed without major complications and should be undertaken unless there is life-threatening large airways obstruction.
Amul, 46 years: Primary cancers that frequently lead to wound problems include breast cancer, skin cancers, soft tissue sarcomas, or soft tissue manifestations of other cancers. Both exogenous and endogenous factors have the capacity to elicit itch (Hgermark, 1992; Wallengren, 1993). This would be classified as mixed pain or a more useful term to aid management may be whether the pain is more or less neuropathic in nature (Bennett et al.
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