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This declaration was formulated by consensus of the various government agencies and other organizations involved. It is hoped that it will be widely circulated.
This article represents the contributions of the panel on "Neuropsychiatric Syndromes and Psychological Symptoms" of the National Cancer Institute of Canada Workshop on Symptom Control and Supportive Care in Patients with Advanced Cancer. The panel's presentations focused on mood disorders and cognitive disorders, and described the current state of knowledge regarding prevalence, assessment, and intervention. Recommendations for future research are presented based on a consensus of the panel as to the need to fill glaring gaps in our current state of knowledge, and a desire to improve the quality of research in this area of palliative medicine. Recommendations for future research on neuropsychiatric symptoms and syndromes in palliative care include (1) adoption of uniform terminology (taxonomy of disorders) and diagnostic classification systems, (2) utilization of existing validated tools and measures in prevalence and intervention research, (3) development of new tools and measures that are more applicable and relevant to the palliative care setting, (4) encouragement for studies of the prevalence of neuropsychiatric symptoms and syndromes, (5) promotion of intervention studies utilizing pharmacologic and nonpharmacologic treatments for depressive disorders and cognitive disorders in advanced cancer patients, and (6) expansion of the focus of such research to other neuropsychiatric disorders (for example, anxiety disorders, posttraumatic stress disorders, and sleep disorders), symptoms (fatigue and tension) and related issues (suicidal ideation and desire for hastened death).
The National Cancer Institute (Canada) sponsored a workshop on symptom control in Banff, Alberta, in October 1993. This article reports on the workshop recommendations for research on one symptom complex, the cachexia-anorexia-asthenia syndrome. In addition to encouraging study generation, the recommendations provide a baseline for assessing the scope and strength of future Canadian research initiatives on cachexia-anorexia-asthenia.
We report a case that illustrates methylphenidate's (MP) usefulness in the management of psychological distress and associated somatization in the palliative-care setting. A 60-year-old man affected by terminal cancer of the prostate had been complaining of increasing physical pain, without any evidence of significant disease progression, opioid toxicity, or previous history of drug addiction. Because of patient's denial, the team had been unsuccessful in identifying any potential emotional factors affecting his physical suffering. MP could both counteract opioid-induced sedation and improve pain control through a positive action on patient's mood. In spite of a rapid development of tolerance, which required a subsequent escalation in MP daily doses, the drug was well tolerated and the patient could die in good physical comfort 2 weeks later.
Hypercalcemia of malignancy is most commonly due to the effects of parathyroid hormone-related peptide, which acts as a humoral factor to cause generalized osteoclast-mediated bone resorption and reabsorption of calcium by the kidney tubule, and may also act as a local resorptive factor adjacent to bone metastases. Local resorptive mechanisms are less common causes of malignant hypercalcemia than previously believed. Treatment begins with intravenous fluid rehydration, followed by a furosemide diuresis and the bisphosphonate pamidronate, 60-90 mg, intravenously. Gallium nitrate is an efficacious but inconvenient alternative to pamidronate. Calcitonin combined with pamidronate is a reasonable initial therapy for severe hypercalcemia to hasten normalization of the serum calcium. Steroids should be reserved for hypercalcemia due to tumor production of 1,25 dihydroxyvitamin D, or for steroid-responsive malignancies. Oral or parenteral bisphosphonates can be used to maintain normocalcemia. In addition to improving the morbidity of acute hypercalcemia, bisphosphonate therapy has been shown to reduce bone pain and pathological fractures in patients with bone metastases, and calcitonin also has a potent analgesic effect in these patients. Treatment for hypercalcemia should therefore be considered in the majority of patients in the palliative care setting.
Between March 27 and 29, 1994, a group of representatives of 32 palliative care programs from eight Latin American countries met under the auspices of the World Health Organization (WHO) Palliative Care Program for Latin America in Florianopolis, Brazil. The participants included physicians, nurses, psychologists, volunteers, drug regulators, hospital administrators, and representatives from the pharmaceutical industry. A comprehensive report by David Joranson (University of Wisconsin-Madison) was followed by a general discussion moderated by Jan Stjernsward, Chief of the Cancer Unit, World Health Organization, and by Eduardo Bruera, Coordinator of the WHO Cancer Pain and Palliative Care Program for Latin America. A number of issues related to opioid availability were identified and discussed. This declaration summarizes the main conclusions of the meeting. The attendants would like to encourage the widest possible distribution of this document.
In late 1990, it became standard practice at the palliative care unit of the Edmonton General Hospital to regularly administer the Mini-Mental State Questionnaire (MMSQ) and to undertake opioid rotation and hydration upon detection of cognitive failure. We retrospectively reviewed the charts of 117 and 162 patients admitted in 1988-1989 and 1991-1992, respectively, to assess the impact of these maneuvers on the prevalence of agitated impaired mental status (IMS). All patients underwent regular cognitive assessment in 1991-1992 versus none in 1988-1989. Seventy-three percent of patients received hydration in the second period versus 32% in the first (P < 0.01). The frequency of opioid rotation was also greater in the second period (41% versus 21%, P < 0.001). The incidence of agitated IMS decreased from 26% in 1988-1989 to 10% in 1991-1992 (P < 0.001). This was reflected by a lower mean dose of the major drug used to treat this condition, haloperidol (3.6 +/- 2.4 versus 5.6 +/- 3.8 mg/day, P < 0.01), and less frequent use of other neuroleptics and benzodiazepines (0.12 versus 0.38 prescriptions per patient, P < 0.01) in the second period. Our data suggest that routine cognitive monitoring, opioid rotation, and hydration may reduce the incidence of agitated IMS in terminal cancer patients.
A 59-year-old woman with metastatic breast cancer experienced a poor response to increasing doses of hydromorphone, possibly related to the neuropathic nature of her pain. Ultimately, the cost of this treatment was more than $1000 per day. Administration of methadone, initially as an adjuvant and eventually as the sole analgesic, at a much smaller dose than expected resulted in very satisfactory analgesia, without the development of serious side effects. In addition, the cost of treatment decreased to less than $25 per day. This case illustrates the rationale and advantages for the use of methadone. Intraindividual variability in the response to various opioids is a factor to be considered when selecting analgesics. Methadone is a useful second-line or third-line opioid for the patient who is highly tolerant to other opioids, as it may demonstrate incomplete cross-tolerance with other agonist opioids. Switching of the opioid to methadone may be a worthwhile option to consider in managing patients who are highly tolerant to other opioids.
Acute renal failure due to bilateral ureteral obstruction is a common problem in palliative care. We report on two patients with advanced rectosigmold carcinoma in which bilateral malignant ureteral obstruction was managed by pharmacological and endourologic methods, respectively. The first patient showed excellent response to high-dose corticosteroids. The second patient showed no evidence of response and a urinary diversion procedure was performed. Indications for both pharmacological and endourological interventions in these patients are discussed. Our findings suggest that decision regarding the management of ureteral obstruction needs to be highly personalized and follow careful discussion with the patient and/or family.
Methadone is a synthetic opioid with excellent oral bioavailability, variable, but long duration of action and extremely low cost. Our group has found that methadone is well tolerated in patients with difficult pain syndromes who are receiving high dose opioids. However, because of high interpersonal variation in bioavailability and the long duration of action of this drug, treatments should be highly personalized. We report on a 61 year old cancer patient who was switched from 84 mg/day of subcutaneous hydromorphone to 90 mg/day of oral methadone. On this dose, she developed respiratory depression and non-cardiogenic pulmonary edema that responded to subcutaneous naloxone and methadone discontinuation. Our findings suggest that standard equalanalgesic tables are unreliable for methadone titration. Switchovers should take place slowly and in a personalized fashion.
Two hundred and seventy-seven patients were admitted to this prospective multicenter study in order to assess the accuracy of a staging system for cancer pain. The staging system (SS) was completed by a trained physician during the initial consultation. This system included the assessment of pain mechanism (PM, neuropathic versus nonneuropathic), pain characteristic (PC, continuous versus incidental), previous opioid dose (OD), cognitive function (CF), psychological distress (PD), tolerance (T), past history of alcohol or drugs (A). During day 21, a final assessment of pain control was made. Agreement for staging was observed in 96% of cases for investigators 1 and 2 (kappa 0.76, P < 0.001), and in 84% of cases between investigators 1 and 3 (kappa 0.723, P < 0.001). Of 276 evaluable patients, 86/92 Stage I (good prognosis) patients achieved good PC (93%) versus 102/184 Stage II and III (poor prognosis) patients (55%, P < 0.001). Sensitivity and specificity of the system were found to be 0.93 and 0.46, respectively. Univariate correlation found significant correlation between pain control and all variables except CF. In logistic regression, CF and OD showed no significant correlation. We, therefore, propose a more simple SS of five categories (PM, PC, PD, T, and A) and two stages (good and poor prognosis). We conclude that the SS is highly accurate in predicting patients with good prognosis, but patients with "poor prognosis" can still achieve good pain control in more than 50% of cases.
The purpose of this randomized, double-blind study was to compare 300 units of hyaluronidase per one-half liter to 150 units per one-half liter in patients receiving brief infusions for subcutaneous hydration. Twenty-five evaluable patients were randomized to receive a local injection of 300 units of hyaluronidase or 150 units of hyaluronidase immediately before two 1-hr infusions of two-thirds dextrose 5% and one-third normal saline solution (500 cc volume). The following day a crossover took place, and patients received the alternate treatment before each of the two 1-hr infusions. The intensity and swelling as reported by the patient (visual analogue scale 0-100), and the intensity of edema and rash as assessed by the investigator (score 0-4) were not significantly different between groups. The patients' and investigators' final choice was also not significantly different. Patients could not distinguish between bolus and their previous experience with overnight clysis. Our results suggest that brief infusions are well tolerated for subcutaneous hydration of patients with advanced cancer. A concentration of 150 units of hyaluronidase per one-half liter is well tolerated in this population.
The purpose of this retrospective study was to determine the prevalence of alcoholism among terminally ill cancer patients when assessed by multidisciplinary interviews and by the CAGE Questionnaire. We reviewed the charts of 100 consecutive patients assessed by a multidisciplinary team for the presence of alcoholism during 1989, and 100 consecutive patients assessed by the CAGE Questionnaire during 1992. Alcoholism was diagnosed in 28/100 patients during 1989 (28%) and 18/66 patients during 1992 (27%). Thirty-four patients were unable to complete the CAGE Questionnaire in 1992 because of sedation or cognitive impairment; six of these patients (17%) were found to be alcoholics after multidisciplinary assessment. Only 9/28 (32%) and 8/24 (33%) patients diagnosed as alcoholics during 1989 and 1992, respectively, had been previously diagnosed as alcoholics according to the medical charts. The mean equivalent daily dose of morphine during admission and on Day 2 during 1992 were 153 +/- 193 mg and 183 +/- 198 for alcoholic patients, versus 58 +/- 80 and 70 +/- 79 mg for nonalcoholics (P = 0.06 and 0.03, respectively). The maximal dose of opioid and the pain intensity during admission, however, were not significantly different between alcoholics and nonalcoholics. Our results suggest that alcoholism is highly prevalent and underdiagnosed among symptomatic terminally ill cancer patients. The CAGE Questionnaire should be used for screening for alcoholism in this population. When multidimensional assessment and management of pain is applied, the outcome of alcoholic patients appears to be similar to that of nonalcoholics.
Tolerance to the analgesic effect of opioids is a poorly understood phenomenon. While generally accepted to be an uncommon problem, it clearly can present major management difficulties in some patients. This case report illustrates different aspects of tolerance, describes a management approach using different opioids, and provides a focus for discussion of some current developments in understanding and managing this problem.
Accumulation of active (toxic) metabolites of opioids might explain cases of opioid toxicity when high doses are used for long periods of time. Other mechanisms of late toxicity of opioids may be found at the receptor level. Whatever the cause, a change of opioids using equianalgesic doses can be expected to improve symptoms of toxicity in some patients, while maintaining pain control. We reviewed the experience with this technique in patients admitted to the Palliative Care Unit of the Edmonton General Hospital. Of 191 patients, 80 underwent opioid rotation (OR) for cognitive failure, hallucinations, myoclonus, nausea and vomiting, local toxicity, and persistent pain. These leading symptoms improved in 58/80 patients (73%, P < 0.01). Pain control, as measured on a 10-cm visual analogue scale (VAS), improved from 4.4 +/- 2.3 to 3.6 +/- 2.0 (P < 0.004) at a dose significantly lower than that predicted to be equianalgesic (577 +/- 1535 mg before OR versus 336 +/- 593 mg after OR, P < 0.04). We conclude that symptoms of opioid toxicity can be relieved by OR, and that a choice of two or three different opioids is necessary to obtain satisfactory long-term pain control.
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PURPOSE: The aim of this double-blind, double-dummy, crossover study was to compare the efficacy, tolerability, and time of onset of analgesia after the administration of 10 mg of morphine hydrochloride via the oral and rectal routes in opioid-naive cancer patients with pain. PATIENTS AND METHODS: Thirty-four patients with cancer pain and no previous opioid treatment were randomized to receive morphine hydrochloride 10 mg orally or rectally (in the form of a microenema) for 2 days. During days 3 and 4, a crossover took place. The scores of pain, nausea, and sedation (visual analog scale of 0 to 100) calculated as the percentage change from baseline (before opioid administration) were assessed at different intervals up to 240 minutes. The number of vomiting episodes was recorded. Parity tests and analysis of variance (ANOVA) were performed to compare the two administration routes. RESULTS: A significant difference in pain intensity was achieved 10 minutes after rectal administration compared with 60 minutes after oral administration. There was still a significant reduction in pain via the rectal route after 180 minutes versus via the oral route after 120 minutes. No significant difference was observed in the intensity of sedation, nausea, or number of vomiting episodes between the oral and rectal routes. CONCLUSION: A liquid solution of morphine is well absorbed via the rectal route. Rectal morphine is safe, effective, easy to manage, and inexpensive, with a rapid onset of action. Rectal morphine can be considered a valid alternative route for opioid administration and may also be used when rescue doses of morphine are required in patients regularly treated with oral or parenteral opioids.
PURPOSE: A significant number of cancer patients will require an alternate route of morphine administration at some point during their illness. This study compared the clinical efficacy and safety of a novel morphine sulfate controlled-release suppository (MS-CRS) and subcutaneous (SC) morphine in patients with cancer pain. METHODS: Thirty patients with cancer pain were randomized in a double-blind crossover study to MS-CRS every 12 hours or SC morphine every 4 hours for 4 days each, using a 2.5:1 analgesic equivalence ratio. Pain intensity was assessed using a visual analog scale (VAS) and the Present Pain Intensity Index of the McGill Pain Questionnaire. Nausea and sedation were also assessed with a VAS. Evaluations were made by the patient at 8 AM, noon, 4 PM, and 8 PM and rescue morphine consumption recorded. RESULTS: Twenty-three patients completed the study (13 men and 10 women; mean age, 64.0 +/- 2.0 years) and were treated with mean daily MS-CRS and SC morphine doses of 326 +/- 69 mg and 138 +/- 28 mg, respectively. There was a small but significant difference in overall ordinal pain-intensity scores in favor of MS-CRS (0.7 +/- 0.1 v 0.9 +/- 0.1, P = .0459). There were no significant differences between MS-CRS and SC morphine in overall VAS scores for pain intensity (13 +/- 3 v 13 +/- 3 mm), sedation (23 +/- 3 v 25 +/- 4 mm), and nausea (8 +/- 2 v 9 +/- 2 mm). The mean daily rescue analgesic consumption during MS-CRS and SC morphine did not differ significantly (1.2 +/- 0.4 v 1.2 +/- 0.4 doses/d). CONCLUSION: MS-CRS, administered every 12 hours, provides analgesia comparable to SC morphine and represents a reliable, noninvasive alternative method of pain control for patients unable to take oral morphine.