Pharmacologic treatment of cancer pain.
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Analgesics, Opioid↗
Biomedical subjects
E Bruera
Publications and source records attributed to E Bruera.
The frequency and clinical course of cognitive impairment in patients with terminal cancer.
BACKGROUND: Cognitive disorders are among the most frequent psychiatric complications of advanced cancer. This study reviews the frequency and clinical course of cognitive failure in patients with advanced cancer admitted to a palliative care unit. METHODS: In this retrospective study, all 348 patients admitted to the Edmonton General Palliative Care Unit over a period of 26 months were reviewed. The Mini-Mental State Examination (MMSE) was used as a screening tool to assess cognitive functioning and was performed on all patients at the time of admission and once to twice weekly thereafter. In all cases, when cognitive failure was diagnosed, a standardized management protocol was followed. RESULTS: Three hundred and twenty-one patients (92.2%) were evaluable. A total of 1441 MMSEs were performed. Each patient underwent an average of 4.7 +/- 4.26 MMSEs and every patient underwent an MMSE every 4.9 (+/- 3.3) days (median, 3.6 days). The mean age (standard deviation [SD]) of the study group was 64.2 (+/- 12) and the mean +/- SD (median) length of stay was 27 +/- 22 (20.5) days. Two hundred and thirty-one patients (71%) died on the unit. One hundred and forty-two patients (44%) had abnormal MMSE scores (MMSE < 0.8) on admission, whereas 176 patients (55%) had abnormal MMSE scores at the time of death or discharge. Of the 231 patients who died on the unit, 157 (68%) had abnormal MMSE scores prior to death. There was no significant difference in the first MMSE between patients who died and those who were discharged (P = 0.16). Of the 240 patients who underwent 2 or more MMSEs, 99 (41%) had normal initial and final MMSEs, 54 (23%) had normal initial MMSE scores but abnormal final scores, and 62 (26%) had both initial and final abnormal scores. Of the 87 surviving patients with an MMSE score of < 0.8 on admission, 25 (29%) had initial abnormal and final normal scores, indicating an improvement. Twelve of these 25 patients (48%) with abnormal initial scores but normal final scores were discharged versus 52 of 99 patients (53%) with normal initial and final MMSE scores (P > 0.2). Of 124 patients with normal final MMSE scores, 64 (52%) were discharged versus 16 of 116 patients (14%) who had abnormal MMSE final scores (P < 0.0001). CONCLUSIONS: These data suggest that cognitive screening should take place in patients with advanced cancer because cognitive failure is highly prevalent in this population, is reversible in a significant proportion of patients, and the presence of sustained cognitive impairment is a poor prognosticator for discharge. However, these results need to be confirmed in prospective studies.
Cognition Disorders↗
When to treat dehydration in a terminally ill patient?
The need to treat dehydration in terminally ill patients has become a very controversial topic. Numerous reports in the literature illustrate opposing view-points from both clinical and ethical perspectives. Arguments for the maintenance of hydration in terminally ill patients have tended to come from "the traditional medical model". Many health care professionals looking after terminally ill patients have reacted to the generalized use of intravenous fluids in dying patients and the perceived negative effects of this management. Our palliative care group has argued that the viewpoint that dehydration in dying patients is not a cause of symptom distress overlooks commonly reported problems, such as agitated delirium, that can be prevented or reversed by the management of dehydration. This review presents a summary of the traditional arguments, a different perspective on the controversy, biochemical parameters reported in terminally ill cancer patients, recent dehydration research, and the use of hypodermoclysis and rectal hydration. We conclude that the data reported to date are insufficient to allow a final conclusion on the benefit or harm of dehydration in terminally ill patients. Nevertheless, it is worth considering that while some dying patients may not suffer any ill effects from dehydration, there may be others who do manifest symptoms, such as confusion or opioid toxicity, that might be alleviated or prevented by parenteral hydration.
Dehydration↗
Matching the clinical function and symptom status with the expectations of patients with advanced cancer, their families, and health care workers.
Continuous accurate assessment is mandatory for palliative care of good quality. One of the major objectives in palliation is to meet the expectations of patient, family members and care givers. While a number of valid tools for assessing symptoms or function are available, there are unfortunately no recognized instruments for assessing expectations. The mismatch of expectations and the actual situation is a major source of distress and conflict. The present paper describes a simple way of visualizing this distress and conflict graphically. In our experience, this method is helpful in raising awareness of and enabling analysis of distress and conflict in patients, family members, and health care workers. It is also useful in the education of students and members of the palliative care team. It is illustrated with reference to four clinical situations.
Adaptation, Psychological↗
Acute neuropsychiatric findings in a patient receiving fentanyl for cancer pain.
A 62-year-old man receiving subcutaneous fentanyl for the management of cancer pain developed generalized central excitation after an overdose of 5000 micrograms of fentanyl. The patient developed acute confusion, restlessness, generalized myoclonus, visual hallucinations, and hyperalgesia and tremors upon tactile stimulation of the arms or legs. These symptoms rapidly disappeared after the administration of 0.2 mg of naloxone. Within an hour the symptoms reappeared and once again, responded immediately after a second injection of 0.2 mg of naloxone. Our findings suggest that fentanyl overdose can occasionally present with general central irritability that responds to naloxone.
Adenocarcinoma↗
An update on the clinical use of methadone for cancer pain.
Methadone is a synthetic opioid agonist considered a second choice drug in the management of cancer pain. Methadone has a number of unique characteristics including excellent oral and rectal absorption, no known active metabolites, high potency, low cost, and longer administration intervals, as well as an incomplete cross-tolerance with respect to other mu-opioid receptor agonist drugs. For these reasons, methadone has the potential of playing a major role in the treatment of cancer pain. However, its use is limited by the remarkably long and unpredictable half-life, large inter-individual variations in pharmacokinetics, the potential for delayed toxicity, and above all by the limited knowledge of correct administration intervals and the equianalgesic ratio with other opioids when administered chronically. Recent findings suggest that standard equianalgesic tables are unreliable for methadone titration in patients tolerant to high doses of opioid agonists and that switchovers should take place slowly and should be personalized. Future research has to better define the variation in both bioavailability and elimination of methadone in different patient populations, the interaction between methadone and the most commonly used drugs in cancer patients, the type and activity of potential methadone metabolites, and the equianalgesic doses between methadone and the most commonly used opioids.
Administration, Oral↗
Dose ratio between morphine and hydromorphone in patients with cancer pain: a retrospective study.
Morphine (M) and hydromorphone (HM) are commonly used opioid analgesics for cancer pain. Opioid rotation is often necessary in the event of toxicity and/or inadequate analgesia. Equianalgesic reference tables based on single dose comparisons are possibly inadequate for patients on chronic treatment and developing tolerance. This retrospective study of opioid rotation involving M and HM sought to determine the equianalgesic dose ratio for 91 rotations in 74 consecutively evaluable cancer pain patients. Only rotations involving subcutaneous (s.c.-s.c.) and oral (p.o.-p.o.) routes were evaluated. There were 44 rotations from M-HM (34: s.c.-s.c., 10: p.o.-p.o.) and 47 rotations from HM-M (35: s.c.-s.c., 12: p.o.-p.o.). Expressing all ratios as M/HM, the median dose ratios (lower-upper quartiles) for s.c. and p.o. rotations were 4.92 (4.1-5.9) vs. 5.76 (4.9-5.8) for M-HM (P = 0.28, NS) and 4.0 (3.1-4.8) vs. 3.45 (2.8-4.2) for HM-M (P = 0.4, NS), respectively. Pain intensity, as measured on a visual analogue scale (VASP), showed no significant difference between mean values pre- and post-rotation. A unified overall median dose ratio of 4.29 (3.3-5.3, lower-upper quartiles) was calculated by expressing all of the HM-M dose ratios as M/HM and combining them with the dose ratios for all of the M-HM rotations. This suggests a potency ratio of approximately 4.3:1 between M and HM. When expressed as M/HM for dose ratio comparison, the median dose ratio for all HM-M rotations was 3.7 (2.9-4.5, lower-upper quartiles) vs. 5 (4.2-5.9) for M-HM rotations (P = 0.0001), suggesting that the opioid to which rotation is taking place is more potent than our proposed unified overall median dose ratio of 4.29:1 would predict. Our data suggests that HM is 5 times more potent than M when given second (M-HM), but is only 3.7 times more potent when given first (HM-M). We therefore recommend a ratio of 5 for M/HM in rotating from M to HM and ratio of 3.7 for M/HM when rotating from HM to M in patients exposed to chronic dosing of these opioids. There was no correlation observed between M-HM and HM-M dose ratios and the level of previous opioid dose, in contrast to HM to methadone rotation where the dose ratio was higher in patients receiving higher doses of HM.
Aged↗
The Edmonton Functional Assessment Tool: preliminary development and evaluation for use in palliative care.
The purpose of this article is to report the development and psychometric testing of the Edmonton Functional Assessment Tool (EFAT). The EFAT was developed as a functional outcome measure for use with a palliative care population. The assessment identified ten functional activities important to patients even in the terminal stage of their illness. In addition, a global performance status rating (PS) asked for an overall judgment of functional status after the ten EFAT functions were evaluated. Tests for interrater reliability and concurrent validity were conducted on a sample of 25 inpatients on the Palliative Care Unit (PCU) at the Edmonton General Hospital (EGH) who were evaluated independently by two raters. Interrater reliability of the EFAT expressed as an intraclass correlation (ICC) was established at 0.88. The interrater reliability of these two raters was 0.71 for the Karnofsky Performance Status (KPS) and 0.81 for the performance status measure of the Eastern Cooperative Oncology Group (ECOG). Concurrent validity of the EFAT was demonstrated by correlating the total EFAT score with the KPS (r = -0.79, P = 0.0001) and the ECOG (r = 0.85, P = 0.0001). The total EFAT score was also strongly correlated with the global PS rating scale (r = 0.90, P = 0.0001). Construct validity of the EFAT was tested with a sample of 101 patients admitted to the unit, which was later divided into the unit group (N = 88) and the home group (N = 13). Our findings provided initial evidence that the EFAT distinguished between the functional status of these two groups. The results of this preliminary study suggest that the EFAT requires further research and development, but shows potential to evolve as a useful clinical tool in palliative care.
Aged↗
Opioid availability in Latin America: the Santo Domingo report progress since the Declaration of Florianopolis.
The World Health Organization (WHO) has indicated that opioid analgesics are insufficiently available, particularly in developing countries, due to a variety of reasons, including legislative, educational, and policy issues. In its effort to promote the rational use of medical opioids and the adequate treatment of patients with cancer, WHO has sponsored a meeting of Latin American representatives every 2 years, which includes health professionals and government regulators. During March 24-27, 1996, a group of 86 representatives of cancer pain relief and palliative care programs from nine Latin American countries met in Santo Domingo under the auspices of the WHO Palliative Care Program for Latin America. For the first time since the First Latin American Meeting, government regulators were present to help address the issue of opioid availability from their perspective. During the meeting, issues pertaining to cancer pain, opioid availability, and palliative care were discussed. This report summarizes some of the events and presents a summary of the conclusions of an earlier meeting in 1994, as described in the Declaration of Florianopolis, and presents its follow-up, The Santo Domingo Report, generated following the 1996 meeting.
Analgesics, Opioid↗
Dyspnea: pathophysiology and assessment.
Dyspnea is frequently a multicausal and devastating symptom among advanced cancer patients. It occurs in 21%-78.6% of patients days or weeks before death and is often difficult to control. The genesis and pathophysiology of dyspnea as a symptom still has not been well understood. Dyspnea is frequently associated with abnormalities in the mechanisms that regulate normal breathing; however, the actual expression of dyspnea by a patient results from a complex interaction between the abnormalities in breathing and the perception of those abnormalities in the central nervous system. The production of dyspnea has to be related to the activation of mechanoreceptors both in the respiratory muscles and in the lung, even in the absence of increased muscle respiratory activity. Respiratory muscle weakness appears to be an important cause of dyspnea in malnourished, asthenic, and cachectic cancer patients. This might also explain why about 24% of dyspneic cancer patients do not present cardiac/pulmonary disease. In addition, two other possible mechanisms of dyspnea have been proposed: chemoreceptor stimulation and efferent activity from the respiratory center by direct ascending stimulation. These factors and the assessment tools used in patients with chronic dyspnea are summarized in this review.
Disease Progression↗
Successful management of multiple enterocutaneous fistulas in a patient with metastatic colon cancer.
Enterocutaneous fistula development is not uncommon in patients with advanced cancer and can be very challenging to manage. The authors present a case study of a patient with multiple enterocutaneous fistulas that developed in the setting of metastatic colon cancer. Assessment methods and interventions that permitted successful management are discussed with emphasis on the value of multidisciplinary care.
Colonic Neoplasms↗
A randomized, controlled trial of intravenous clodronate in patients with metastatic bone disease and pain.
To evaluate the effectiveness of intravenous clodronate in ameliorating refractory bone pain in patients with metastatic bone disease, 60 patients with established osseous metastases and persistent bone pain were randomized to receive either clodronate (600 mg or 1500 mg in 500 mL of normal saline) or 500 mL of saline as placebo. After 2 weeks, the patients were crossed over to receive the alternate treatment. After another 2 weeks, each patient and investigator made a blinded choice. Daily visual analogue scales (VAS) and analgesic diaries were recorded throughout the study period. Forty-six patients were evaluable (77%). A treatment x period interaction was identified in the VAS and daily morphine equivalent dose (DMED) scores. First period analysis of the VAS scores for general pain, pain at rest, and pain upon movement demonstrated an average reduction of 13, 14, and 24 mm, respectively, from baseline, but were not significantly different from changes following placebo. The average change in DMED was -6.4 (SE = 2.9) following clodronate and was +24.6 (SE = 14.9) following placebo (p = 0.03). In the blinded choice of which agent resulted in improvement in pain, 26 (57%) patients chose clodronate, 12 (26%) chose placebo, and eight (17%) had no preference (p = 0.0021). For the investigators who also made a blinded selection, clodronate was chosen in 30 (65%) patients, placebo in ten (22%) patients, and no difference was apparent in six (13%) (p < 0.0001). Intravenous clodronate appeared to have analgesic effect in patients with refractory bone pain due to metastatic bone disease. The optimal dose and duration of effect require further evaluation, particularly in patients with stable disease and persistent bone pain.
Adult↗
Is a "palliative" patient always a palliative patient? Two case studies.
Review of the literature suggests that misdiagnosis of terminal illness is infrequent. In the first 6 months of the recently established Edmonton Regional Palliative Care Program, two of 330 referrals proved to be in the category of erroneous diagnosis of terminal disease. These two cases are reported, along with discussion of aspects of the time-honored usefulness of careful history and physical examination. This experience highlights the importance of assessment, investigation, and aggressive therapy, even in "terminal" patients, including those in the geriatric population.
Acute Kidney Injury↗
Severe opioid toxicity and somatization of psychosocial distress in a cancer patient with a background of chemical dependence.
A case of severe opioid toxicity is described in a 52-year-old cancer patient. The patient presented with classical clinical features of central hyperexcitability associated with opioid toxicity: delirium, myoclonus, hallucinations, hyperalgesia, and a possible seizure. This patient had a background of severe psychosocial distress and somatization in addition to a history of benzodiazepine dependence and alcohol abuse. The occurrence of opioid toxicity in this patient highlights the risks of a unidimensional approach to cancer pain, which ignores the non-organic components of pain, such as psychosocial distress, which will not respond to escalating doses of opioid medication.
Alcoholism↗
Cancer pain management.
Pain occurs in more than 80% of cancer patients before death. Because of the increase in the frequency of cancer deaths worldwide, it is imperative to address cancer pain as a public health problem. Until recently, educational efforts were focused on treatment issues rather than adequate assessment. The approach to pain intensity as a multidimensional construct has helped in focusing treatments and identifying prognostic factors. Valid tools have been developed that allow multidisciplinary assessment of these prognostic factors and their complex interrelationship with the analgesic response. As a result of increased opioid exposure, patients are currently developing newer toxicities, mostly central excitability including delirium, myoclonus, grand mal seizures, and hyperalgesia. The observation that more than 80% of patients will require alternate routes for opioid delivery before death led to the development of a number of novel and effective alternate routes for delivery. Finally, in recent years it has become evident that some specific pain syndromes need to be addressed using specific assessment and management techniques. Incidental pain, somatization, neuropathic pain, and cancer pain in patients with alcoholism and drug addiction are some of these syndromes.
Analgesics, Opioid↗
Validity of the McGill Quality of Life Questionnaire in the palliative care setting: a multi-centre Canadian study demonstrating the importance of the existential domain.
This study was carried out in eight palliative care services in four Canadian cities. A revised version of The McGill Quality of Life Questionnaire (MQOL) is compared to a single-item scale measuring overall quality of life (SIS), and the self-administered version of the Spitzer Quality of Life Index (SA-QLI), to obtain evidence of validity. MQOL total score predicts SIS better than does SA-QLI, although much of the variance remains to be explained. The results of principal components analysis of data using this revised version of MQOL are similar to those from previous MQOL studies with different patient populations. The MQOL subscales, constructed on the basis of principal components analysis, demonstrate acceptable internal consistency reliability. The MQOL measures reflecting physical well-being and existential well-being are important for predicting SIS.
Humans↗
Euthanasia and physician-assisted suicide: a comparative survey of physicians, terminally ill cancer patients, and the general population.
PURPOSE AND METHODS: There is an ongoing debate about the legalization of euthanasia. The attitudes and beliefs of the general public and physicians appear to differ; the views of patients have not been adequately explored. During 1995, we conducted a simultaneous survey in the province of Alberta, Canada, of a random sample of 1,240 individuals from the general population, 179 physicians, and 62 consecutive patients with terminal cancer. The same instrument was administered to the public and physicians through telephone interview, and to patients in a face-to-face interview. Statements related to the legalization of euthanasia and physician-assisted suicide were scored using 1-to-7 Likert agreement scales. RESULTS: A slight majority of members of the public and terminally ill patients (50% to 60%) agreed with the legalization of euthanasia and assisted suicide, while most physicians (60% to 80%) opposed it. In multivariate analysis, independent associations with support of active end of life measures included the following: group surveyed, strength of religious beliefs, religion (highest support by individuals with no religion), education (lower education associated with higher support), and the perception of burden on families, and physical and emotional suffering by cancer patients. CONCLUSION: In all groups, a marked polarization of attitudes was observed, with most individuals either strongly agreeing or strongly disagreeing with the statements in the survey. Although a slight majority of the public supported euthanasia, one third opposed it. Most physicians opposed these interventions and appeared not to be willing to perform these procedures if legalized. Our findings suggest that legalization at this time could be highly divisive and controversial from a societal perspective.
Adult↗
Dehydration in the terminally ill.
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Dehydration↗