A comparison of patient and proxy symptom assessments in advanced cancer patients.

The purpose of this study was to compare patient and proxy (physician and nurse) assessments of symptoms in advanced cancer patients. The sample consisted of 49 patients with advanced cancer admitted to an acute palliative care unit. Three independent assessments were completed for each patient on two occasions within 11 days of admission. On each occasion, symptoms were rated independently by the patient and two proxies (treating physician and nurse), using the Edmonton Symptom Assessment System (ESAS). The ESAS is a nine-item visual analogue scale (VAS) for assessing pain, activity, nausea, depression, anxiety, drowsiness, appetite, well-being and shortness of breath. Symptom ratings were compared using a repeated-measures ANOVA procedure and correlations. Average physician ratings were generally lower than average patient ratings for both occasions. Average nurse ratings agreed more closely with patient ratings, with a trend towards lower ratings on occasion 1 and higher ratings on occasion 2. There was a significant rater (person rating the effects) effect (P < 0.01) for three of the nine symptoms: physicians rated drowsiness, shortness of breath and pain significantly lower than patients. For drowsiness and shortness of breath, these differences were clinically relevant, representing a difference of more than 12 mm on a 100-mm VAS. The accuracy of assessments amongst those rating the symptoms did not improve over time. Proxy assessments of symptom intensity, particularly by physicians, were significantly lower than patient assessments for three of the nine symptoms. Further research regarding the reliability of patient and proxy assessments is needed to assess and manage symptoms in advanced cancer effectively.

A prospective multicenter assessment of the Edmonton staging system for cancer pain.

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.

Role of rectal route in treating cancer pain: a randomized crossover clinical trial of oral versus rectal morphine administration in opioid-naive cancer patients with pain.

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.

Comparison of the efficacy, safety, and pharmacokinetics of controlled release and immediate release metoclopramide for the management of chronic nausea in patients with advanced cancer.

BACKGROUND: The short elimination half-life of metoclopramide necessitates frequent administration for optimal relief of nausea. This study compares a newly developed controlled release preparation of metoclopramide (CRM) and immediate release metoclopramide (IRM) with respect to efficacy, safety, and pharmacokinetics in patients with chronic nausea associated with advanced cancer. METHODS: Thirty-four patients with advanced cancer with nausea lasting more than 1 month and with no evidence of involvement of the gastrointestinal tract, peptic ulcer or gastritis, brain metastases, or metabolic abnormalities were randomized, in a double-blind cross-over study, to receive 40 mg of CRM every 12 hours or 20 mg of IRM every 6 hours for 3 days. Nausea, food intake, and side effects were assessed four times daily. On Day 3, sequential venous samples were taken (12 patients) to determine plasma metoclopramide concentrations. RESULTS: In 29 evaluable patients, the intensity of nausea on Day 3, measured by a 0-100-mm visual analogue scale and 0-3 categoric scale was 15 +/- 17 and 0.6 +/- 0.6 after IRM, versus 8 +/- 9 (P = 0.033) and 0.4 +/- 0.5 (P = 0.055) after CRM, respectively. Visual analogue scale nausea scores recorded by time of day and by day for the 3 treatment days were significantly lower for patients who received CRM compared with those who received IRM (P = 0.047 and P = 0.043, respectively), but categoric nausea scores were not significantly different between treatments by time of day and by day across the 3 treatment days. No differences were observed in caloric intake or side effects between treatments. In a pharmacokinetic analysis, the CRM/IRM ratio for area under the curve0-12 (microgram x hours x L-1), Cmax (microgram/L), and Tmax (hours) was 100%, 98%, and 2.3 fold, respectively. CONCLUSION: Controlled release metoclopramide is safe and effective in managing chronic nausea in patients with advanced cancer. Future studies should focus on characterizing this syndrome more clearly and on determining the optimal dose of metoclopramide and the effects of drug combinations that have proven to be useful in managing chemotherapy-induced emesis (i.e., metoclopramide plus corticosteroids).

The use of hypodermoclysis for rehydration in terminally ill cancer patients.

The need to treat dehydration in terminally ill patients to minimize symptom distress remains a controversial issue. Hypodermoclysis (HDC) is a simple technique for rehydration that offers many advantages over the intravenous route. In this prospective open study of 100 consecutive patients who died on a palliative care unit, we recorded our indications for, and use of, HDC. Of the 100 patients, 69 received HDC for an average of 14 +/- 18 days during an average admission of 35 +/- 41 days. The 31 patients who did not receive HDC had an average admission of 22 +/- 24 days, and appeared to have different characteristics than the HDC group. HDC was well tolerated in most patients at an average volume of 1203 +/- 505 mL/day. These results confirm that HDC for dehydration is a safe and effective technique and suggest the need for further research to clarify the role of rehydration in assisting symptom control.

Novel photodynamic effects of a benzophenothiazine on two different murine sarcomas.

The photochemotherapeutic properties of a novel benzophenothiazine, 5-ethylamino-9-diethylaminobenzo[a]phenothiazinium chloride, were assessed in vitro and in vivo against two murine mammary sarcoma models (EMT-6 and RIF). Photodynamic therapy (PDT) of EMT-6 and RIF cells following a 30-min incubation with dye (0.4 microgram/ml) and a light dose of 3.3 J/cm2 killed 87.0 and 99.6% of the cells, respectively. Over this same time period, RIF cells accumulate more than twice the amount of dye than the EMT-6 cell line [7.54 +/- 0.17 (SD) versus 3.11 +/- 0.15 nmol/10(6) cells] which probably accounts for their increased sensitivity to PDT. Conversely, in vivo, the EMT-6 tumor accumulates 3 times more dye (34.66 +/- 2.16 micrograms/g dry weight) than the RIF tumor (12.28 +/- 1.27 micrograms of dye/g) 3 h post-s.c. injection of dye (15 mg/kg). A study of the concentration dependent uptake of dye (following s.c. injection) in the tumor and plasma of mice bearing the EMT-6 tumor indicated a nonlinear relationship for both compartments. Maximum tissue uptake of dye and discrimination between tumor and skin or muscle occur 3-8 h following s.c. injection of dye. The ratios of dye in the tumor to the dye in surrounding skin and gastrocnemius muscle 8 h following dye injection were 4:1 and 8:1, respectively. At 24 h after dye injection, the dye was not detectable by absorption spectroscopy in the tumor, skin, or muscle. Decreasing the fluence rate from 200 to 50 mW/cm2 at a total light dose of 100 J/cm2 optimized the PDT effect. At 3 h following s.c. administration of dye, PDT of EMT-6 (7.5 mg of dye/kg; 50 mW/cm2; 100 J/cm2) and RIF tumors (15 mg dye/kg; 50 mW/cm2; 150 J/cm2) resulted in 100 and 70% cures, respectively. Histology at 24 and 72 h post-PDT showed minimal or no damage to the surrounding tissue (skin) while 70-90% of the tumor cells were destroyed or damaged. Moreover, 50-60% of the tumor cells isolated and cultured immediately following PDT were found to be nonviable. Similarly, the administration of 60 mg 5-ethylamino-9-diethylaminobenzo[a]phenothiazinium chloride/kg also resulted in no damage to the skin 24 h following PDT. It is suggested that the redox properties of the dye coupled with the differing metabolic states of the tumor and skin, which increase the amount of photoactive, oxidized dye present in the tumor and decrease it in the skin, are responsible for this unique differential PDT effect.(ABSTRACT TRUNCATED AT 400 WORDS)

Use of the Edmonton Injector for parenteral opioid management of cancer pain: a study of 100 consecutive patients.

In this retrospective study, we reviewed the patterns of use of the Edmonton Injector (EI) in 100 consecutive cancer patients. Seventy-eight patients used the EI for an average of 23 +/- 27 days. The main reasons for starting the EI were nausea (37 patients) and severe pain (31 patients). The median opioid dose equivalent to parenteral morphine (MEDD) was 264 +/- 443 mg/day. The mean duration of the subcutaneous injection site was 6.5 +/- 9.2 days. The most frequent reasons for change were accidental needle pulling (59%) and erythema (12%). Only two patients developed local infection (1% of 196 sites). The average cost of treatment was $1.65 Canadian per patient per day. No mechanical problems or refusals to start or continue treatment were detected. We conclude that the EI is a safe and simple device that allows for cost-effective parenteral administration of opioids for cancer pain.

Local tolerance to subcutaneous infusions of high concentrations of hydromorphone: a prospective study.

In a prospective open study, 24 patients with cancer pain receiving parenteral opioids were administered highly concentrated solutions of hydromorphone in order to assess the local tolerance to the subcutaneous infusion. Patients received a mean concentration of hydromorphone of 30 +/- 15 mg/mL at a mean rate of infusion of 0.3 +/- 0.25 mL/hr. Of 22 evaluable patients, 17 (77%) had a site duration of more than 7 days with their first subcutaneous site (mean concentration of 34 +/- 8 mg/mL of hydromorphone). Four of the five remaining patients (80%) had site duration of more than 7 days with their second subcutaneous site. Only one patient (5%) did not reach a 7-day duration after three consecutive site changes. Out of 7 subcutaneous sites that presented signs of toxicity before 7 days of infusion, the main problem was erythema in three cases, swelling in two cases, and bleeding in two cases. All sites improved spontaneously and did not require any medical treatment. No correlation was found between the concentration or rate of infusion of hydromorphone and the duration of the subcutaneous site. The duration of the site was significantly correlated with weight, tricep skinfold, subscapular skinfold, and age of the patients. Our findings suggest that hydromorphone can be safely administered in concentrations that are much higher than those commercially available. The availability of highly concentrated formulations of different opioids for parenteral use will make home management simpler and cheaper.

Bromocriptine redirects metabolism and prevents seasonal onset of obese hyperinsulinemic state in Syrian hamsters.

Bromocriptine redirects metabolism and prevents seasonal onset of the obese hyperinsulinemic state in Syrian hamsters. Metabolic and hormonal effects of bromocriptine were studied in seasonally obese female Syrian hamsters, Mesocricetus auratus. Daily injections of bromocriptine and vehicle (controls) were made at light onset (10:14-h light-dark cycle) for 10 wk. After 9 wk of treatment blood samples were taken every 4 h during a day for assays of hormones, glucose, triglyceride, and fatty acids, and after 10 wk of treatment, tests were carried out to measure insulin-stimulated glucose disposal during a hyperinsulinemic clamp, lipid mobilization (rate of glycerol appearance), protein turnover (lysine flux and deamination), and body composition (deuterium dilution). Bromocriptine reduced percent body fat by 53% and increased percent lean body mass by 8%. It also decreased triglyceride levels by 52% and plasma free fatty acid concentration during the dark-near light onset by 49% and glycerol appearance by 25%. Protein synthesis and catabolism were increased by 62 and 56%, respectively, and deamination of amino acid was decreased by 53% by bromocriptine. Bromocriptine reduced plasma concentration of insulin throughout the day, especially at light onset, by 78% without change in baseline glucose level and markedly decreased steady state plasma glucose (by 40%) during a continuous infusion of insulin and glucose. It also reduced the nocturnal plasma concentration of prolactin by 90%, cortisol by 70%, and thyroid hormones (thyroxine and triiodothyronine) by 50% and dramatically altered the circadian profiles of these hormones and insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

The use of urinary catheters in terminally ill cancer patients.

Recent reports have commented on the need to improve our knowledge and management of urinary problems in terminally ill patients. We conducted a prospective study in 61 consecutive patients admitted to our palliative care unit (PCU), who were assessed for urinary problems, use of urinary catheters, and management of problems associated with the catheters. A total of 74% (45 of 61) of the patients required a catheter before death, with 23 (38%) being admitted to the PCU with a catheter, and 22 patients (36%) requiring a catheter during admission to PCU. We present our findings regarding the duration of catheter use, indications for catheters, type of catheters used, and complications of catheters. The data collected suggest that, although urinary problems and catheter use are common in terminal illness, if strict guidelines are followed there is no demonstrable mortality, and morbidity associated with catheter use is outweighed by patient benefit.

Symptomatic benefit of supplemental oxygen in hypoxemic patients with terminal cancer: the use of the N of 1 randomized controlled trial.

The symptomatic effects of oxygen on the dyspnea of terminally ill cancer patients have not been clearly established. Therefore, the decision to administer oxygen is frequently made on an individual basis. We report on the use of N of 1 randomized clinical trial to compare the symptomatic benefit of respiratory failure due to terminal ovarian cancer. A 53-yr-old female patient underwent 6 randomized double-blind crossover trials between oxygen 5 L/min delivered by mask and air 5 L/min delivered by mask. Each treatment period lasted 5 min. The mean saturation of oxygen during the baseline period was 84% +/- 3%, versus 84% +/- 4% on air (P,NS) and 94% +/- 4% on oxygen (P less than 0.001). The mean visual analogue scale (VAS) for dyspnea was 77 +/- 4 during the baseline period as compared to 51 +/- 7 after air (P less than 0.001), and 40 +/- 5 after oxygen (P less than 0.001). The patient and the investigator chose oxygen blindly in 5 of 5 cases, air in 0 and 1 case, and no choice was made in 1 and 0 case, respectively. In 4 cases the patient considered the difference between oxygen and air to be of "much importance," and in one case to be of "moderate importance." No significant treatment, period, or interaction between period and treatment was detected for the difference in the VAS. We conclude that oxygen was significantly better than air for symptomatic improvement in this patient. The N of 1 technique is a simple and reliable method for the assessment of individual patients' response to oxygen.

Estimate of survival of patients admitted to a palliative care unit: a prospective study.

In a prospective open study, 61 consecutive patients with advanced cancer admitted to a Palliative Care Unit underwent survival estimation by two independent physicians after a complete medical exam performed during the first day of admission. An independent research nurse also assessed each patient during the first day of admission. The assessment included activity, pain, nausea, depression, anxiety, anorexia, dry mouth, dyspnea, dysphagia, weight loss, and cognitive status. After the assessment was completed, patients were followed until discharge or death. In 47 evaluable patients, logistic regression showed a significant correlation between survival and dysphagia, cognitive failure, and weight loss. Accordingly, an "indicator of poor prognosis" was considered to exist in any patient who demonstrated weight loss of 10 kg or more plus cognitive failure (Mini-Mental State Questionnaire less than 24) plus dysphagia to solids or liquids. This indicator had a similar level of sensitivity, specificity, and overall accuracy, and a higher level of significance as compared with the assessment by physician #1 and physician #2, respectively. Our data suggest that three simple determinations, which may be performed by a nurse, can predict survival more or less than 4 wk as well as the assessments of two skilled physicians. These results need to be confirmed in other trials with large numbers of patients. Perhaps confirmation of these results and identification of other prognostic factors will result in staging systems for survival estimation of terminally ill cancer patients.

Symptom control during the last week of life on a palliative care unit.

A recent report suggested that more than 50% of terminal cancer patients have physical suffering that requires sedation in the last days of life. To evaluate this finding on our 14-bed palliative care unit, a retrospective analysis of 100 consecutive patients admitted for 6 days or more was carried out. Information was collected on major symptoms requiring treatment, symptom control at admission and during each of the last 7 days of life, medications used, and changes that may have contributed to sedation. Of the 100 patients, 99 had pain, 46 had dyspnea, 71 had nausea, and 39 experienced delirium. Visual Analogue Scores (VAS) were done twice a day in all patients; mean pain showed a change from 31 +/- 24 on Day 6 to 24 +/- 19 on day of death (DOD) (p less than 0.05); nausea from 19 +/- 18 on Day 6 to 13 +/- 9 on DOD (p less than 0.01); drowsiness from 51 +/- 28 on Day 6 to 85 +/- 45 on DOD (p less than 0.001); symptom distress score from 49 +/- 11 on Day 6 to 52 +/- 9 on DOD (p less than 0.01). On the day of admission (DOA), 69% of VAS were done by the patient and 28% by the nurse as compared to 8% by the patient and 90% by the nurse on DOD. Level of consciousness on DOA was alert (72%), drowsy (28%), unresponsive (0%) and by DOD was alert (2%), drowsy (41%), unresponsive (57%).(ABSTRACT TRUNCATED AT 250 WORDS)