R. Neil MacDonald

The cognitive effects of the administration of narcotic analgesics in patients with cancer pain

&NA; Forty patients with cancer pain receiving intermittent narcotics were admitted to a prospective study designed to assess the cognitive effects of narcotics. Twenty patients had undergone no change in narcotic dose or type ⩾ 7 days (stable dose, SD, group), and 20 patients had undergone an increase of ⩾ 30% in dose ⩽ 3 days before (increased dose, ID, group). Age, primary tumor, type, dose and route of narcotic were not different between the SD and ID group. Cognitive tests (finger tapping, FT, 10 and 30 sec, arithmetics, A, reverse memory of digits, RM, and visual memory, VM) were performed in all patients before and 45 min after their morning dose of narcotics for 2 consecutive days. Mean percentual change in FT 10 sec, FT 30 sec, A, RM, and VM after the narcotic dose were 97 ± 9%, 100 ± 14%, 100 ± 13%, 100 ± 15%, 98 ± 19%, in the SD group, vs. 77 ± 14% (P < 0.001), 83 ± 13% (P < 0.001), 124 ± 21% (P < 0.001),60 ± 21% (P < 0.001) and 68 ± 21% (P < 0.001) in the ID group, respectively. Our results suggest that patients who undergo a significant increase in the dose of intermittent narcotics experience significant cognitive impairment, that disappears after 1 week of the increase. More research is needed to better characterize the cognitive toxicity of intermittent narcotics, and to determine the cognitive effects of long acting narcotics, continuous infusions, or of the addition of amphetamines.

Effects of morphine on the dyspnea of terminal cancer patients

We report an open, uncontrolled study designed to assess the effects of subcutaneous (SC) morphine on dyspnea of terminal cancer. Twenty patients with dyspnea caused by restrictive respiratory failure received an SC dose of morphine of 5 mg (5 patients who were not receiving narcotics), or equivalent to 2.5 times their regular dose (15 patients who were receiving narcotics for pain). Dyspnea (D) and pain (15 cases) were measured before the dose and every 15 min for 150 min after the injection using a visual analog scale 0-100. Respiratory rate (RR), respiratory effort (RE) (score 1-6), arterial saturation of O2 (SO2) and end-tidal PACO2 were determined before and 45 min after SC morphine. D, RR, RE, SO2, and PACO2 were 68 +/- 32, 32 +/- 7; 3.5 +/- 1.8, 87 +/- 10, and 31 +/- 12, respectively, before SC morphine, and 34 +/- 25 (P less than 0.001), 31 +/- 9 (P:NS), 3.2 +/- 1.9 (P:NS), 86 +/- 11 (P:NS), and 33 +/- 9 (P:NS), respectively, 45 min after SC morphine. Nineteen of 20 patients (95%) reported improved dyspnea after morphine. We conclude that morphine appears to improve dyspnea without causing a significant deterioration in respiratory function in terminal cancer patients. Double-blind placebo controlled studies are needed in this population.

Use of methylphenidate as an adjuvant to narcotic analgesics in patients with advanced cancer

Abstract Between October 1984 and July 1987, 50 patients were treated with methylphenidate (MP) for narcotic-induced sedation. All patients had pain due to advanced cancer and were receiving a mean daily equivalent dose of morphine of 165 ± 30 mg/day. Methylphenidate was started at a dose of 15 mg/day. Two patients (4%) had acute toxicity (hallucinations and paranoid-aggressive reaction, respectively) and required discontinuation of the drug. Forty-four of the 48 (91 %) remaining cases reported improvement after 48 hr of treatment and continued on MP for 39 ± 20 days. No other patient needed to discontinue MP because of toxicity. The mean maximal daily dose of MP and narcotics was 42 ± 6 mg and 237 ± 62 mg, respectively. The main reason for discontinuation of MP was a decrease in the dose of narcotics (18 cases); 12 patients continued to take MP until time of death. We conclude that: (1) MP can be administered to carefully selected advanced cancer patients with good tolerance; (2) toxicity occurs very early in the treatment, and late toxicity is infrequent; (3) significant tolerance develops to MP over the period of a month.

A double-blind, crossover trial of intravenous clodronate in metastatic bone pain

After a baseline symptom and laboratory assessment, 24 patients with metastatic bone disease and pain were randomized to receive either a 4-hr intravenous infusion of 2-dichloromethylene bisphosphonate (Cl2MDP), 600 mg in 500 mL of normal saline, or a 4-hr placebo infusion, 500 mL of normal saline. The administration was double blind. After 1 wk, the assessment was repeated and the patients were crossed over to the alternate treatment. After 1 more wk, a final assessment and blinded choice by the patient and investigator took place. Of the 21 evaluable patients, 12 (57%) chose the Cl2MDP and 4 (19%) chose the placebo; 5 (24%) patients did not have a specific preference (p = NS). The investigator chose the Cl2MDP in 14 (67%) cases, placebo in 6 (29%) cases and was unable to discern a difference in 1 (5%) case (p less than 0.05). The patients and investigator made similar selections in 16 (76%) instances. On the visual analogue scale assessments, a significant decrease in pain scores was observed following the Cl2MDP infusion (p less than 0.01) and an increase in activity scores was also demonstrated (p less than 0.01). No significant difference in the daily oral morphine equivalent analgesic requirement was demonstrated for either arm. No difference in clinical and laboratory parameters of toxicity was evident between the placebo and Cl2MDP arms of the trial. Our preliminary findings suggest that Cl2MDP is safe, and has analgesic properties that may prove to be useful in the management of metastatic bone pain.

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.

Association between asthenia and nutritional status, lean body mass, anemia, psychological status, and tumor mass in patients with advanced breast cancer

Sixty-four consecutive patients with advanced breast cancer were included in a study designed to determine the prevalence of asthenia and its association with other clinical features. The Asthenia Score (AS, the average of four tests designed by our group to assess asthenia) was 59 +/- 9 for patients versus 88 +/- 7 for a group of 68 normal controls (p less than 0.001). Twenty-six patients (41%) scored below the tenth percentile of normal controls and were considered asthenics. AS was correlated with depression and the general severity index of the SCL-90 R test. No association was found between AS and nutritional status, lean body mass, tumor mass, anemia, or type of treatment. We conclude that asthenia is a frequent symptom in patients with advanced breast cancer, which, in our series, showed independent correlations only with psychological distress.

Nutrition in cancer patients: an update and review of our experience

Abstract Malnutrition is one of the most frequent complications of advanced cancer. During recent years, many papers have addressed the incidence and causes of malnutrition in cancer patients, as well as its treatment with such measures as parenteral nutrition, nasogastric infusions, or appetite stimulants. We review this literature and provide a practical approach for the nutritional management of the patient with advanced cancer.Malnutrition is one of the most frequent complications of advanced cancer. During recent years, many papers have addressed the incidence and causes of malnutrition in cancer patients, as well as its treatment with such measures as parenteral nutrition, nasogastric infusions, or appetite stimulants. We review this literature and provide a practical approach for the nutritional management of the patient with advanced cancer.

Asthenia in Patients with Advanced Cancer

Abstract Asthenia is a clinical syndrome characterized by generalized weakness as well as physical and mental fatigue. It occurs in more than two thirds of patients with advanced cancer. Although it is a multi-causal syndrome, most of the evidence points to structural or functional abnormalities in the muscles as the main mechanism of asthenia. These changes are probably due to a substance or group of substances produced by the presence of the tumor. In the minority of patients, for whom a treatable contributing factor to the asthenic syndrome is identified, its correction can produce a major improvement. In the majority of patients, for whom the cause of asthenia remains unknown, only symptomatic treatment can be tried. Both corticoids and amphetamines have been used in selected populations with partial success. Research is needed in order to better define the incidence and severity of asthenia in cancer patients, to establish its most frequent cause, and to develop useful treatments for this syndrome.

Influence of the pain and symptom control team (PSCT) on the patterns of treatment of pain and other symptoms in a cancer center

To assess the influence of a pain and symptom control team on the pattern of prescription of pharmacologic and nonpharmacologic treatments for cancer pain, we reviewed the charts of 100 consecutive patients admitted to the Cross Cancer Institute during 1987 and 100 patients admitted during 1984. The average daily dose of parenteral morphine per patient was 44 +/- 26 mg in 1987 versus 34 +/- 38 mg in 1984 (p less than 0.05). In 1987 and 1984, only 31 and 22% of the analgesics were ordered around the clock respectively (P:NS). Approximately half of the patients in 1987 and 1984 were prescribed antiemetics and two-thirds of the patients were prescribed laxatives. Parenteral narcotics were prescribed subcutaneously in 0/52 cases in 1984 versus 21/63 cases in 1987 (33%, p less than 0.01). The pattern of prescription of narcotics by residents changed significantly during the last four weeks of rotation as compared to the first four weeks. We conclude that there have been some changes in the modality of treatment of pain that are probably due to changes in the pattern of prescription by the residents and continued improvement in assessment of pain by nurses. However, in several areas of treatment the impact of a pain and symptom control team remains minimal.

Decreased local toxicity with subcutaneous diamorphine (heroin): a preliminary report

We report the cases of 5 patients who developed severe local toxicity during the subcutaneous administration of morphine sulphate and hydromorphone hydrochloride. All patients required site changes more frequently than once every 24 h due to redness, swelling, or pain while receiving morphine or hydromorphone. All patients showed prolongation in the duration of sites of infusion once an equianalgesic dose of diamorphine hydrochloride (heroin) was started. No change in pain control or systemic toxicity was detected with diamorphine. These findings suggest that diamorphine could be a useful alternative for patients who develop severe toxicity to subcutaneous morphine or hydromorphone.