Karen Broadley

A systematic review of the use of opioids in the management of dyspnoea

Background: Opioids are commonly used to treat dyspnoea in palliative medicine but there has been no formal evaluation of the evidence for their effectiveness in the treatment of dyspnoea. A systematic review was therefore carried out to examine this. Methods: The criteria for inclusion required that studies were double blind, randomised, placebo controlled trials of opioids for the treatment of dyspnoea secondary to any cause. The methods used to identify suitable studies included electronic searching of the literature, hand searching of the literature, and personal contact with relevant individuals and organisations. Random effects meta-analyses were performed on all included studies and on various subgroups (studies involving nebulised opioids or patients with chronic obstructive pulmonary disease (COPD)). Subgroups were compared using meta-regression. Some studies included in the systematic review could not be included in the meta-analysis because insufficient data were presented. Results: Eighteen studies fulfilled the criteria for the review. The meta-analysis showed a statistically significant positive effect of opioids on the sensation of breathlessness (p=0.0008). Meta-regression indicated a greater effect for studies using oral or parenteral opioids than for studies using nebulised opioids (p=0.02). The subgroup analysis failed to show a positive effect of nebulised opioids on the sensation of breathlessness. The results of the subgroup analysis of the COPD studies were essentially similar to the results of the main analysis. Conclusion: This review supports the continued use of oral and parenteral opioids to treat dyspnoea in patients with advanced disease. There are insufficient data from the meta-analysis to conclude whether nebulised opioids are effective, but the results from included studies that did not contribute to the meta-analysis suggest that they are no better than nebulised normal saline.

Fatigue in advanced cancer: a prospective controlled cross-sectional study.

SummaryUncontrolled studies have reported that fatigue is a common symptom among patients with advanced cancer. It is also a frequent complaint among the general population. Simply asking cancer patients whether or not they feel fatigued does not distinguish between the ‘background’ level of this symptom in the community and any ‘excess’ arising as a result of illness. The aim of this study was to determine the prevalence of fatigue among palliative care inpatients in comparison with a control group of age and sex-matched volunteers without cancer. In addition, the correlates of fatigue were investigated. The prevalence of ‘severe subjective fatigue’ (defined as fatigue greater than that experienced by 95% of the control group) was found to be 75%. Patients were malnourished, had diminished muscle function and were suffering from a number of physical and mental symptoms. The severity of fatigue was unrelated to age, sex, diagnosis, presence or site of metastases, anaemia, dose of opioid or steroid, any of the haematological or biochemical indices (except urea), nutritional status, voluntary muscle function, or mood. A multivariate analysis found that fatigue severity was significantly associated with pain and dypnoea scores in the patients, and with the symptoms of anxiety and depression in the controls. The authors conclude that subjective fatigue is both prevalent and severe among patients with advanced cancer. The causes of this symptom remain obscure. Further work is required in order to determine if the associations reported between fatigue and pain and between fatigue and dyspnoea are causal or coincidental.

A prospective survey of the use of dexamethasone on a palliative care unit

One hundred and six consecutive patients started on glucocorticosteroids (steroids) according to a defined prescription policy were surveyed each week to document the indications for use, any beneficial effect, any toxicity incurred and the reason for stopping. All patients had advanced malignant disease and survived for a median of 40.5 days (range 1–398+ days) from the start of steroid treatment. Fifty-seven per cent of patients completed three or more assessments. The most common specific indications for starting steroids were spinal cord compression, cerebral metastases, lymphangitis carcinomatosa and intestinal obstruction. The most common non-specific indications were anorexia, nausea, low mood, pain and vomiting. The median duration of steroid use was 21.5 days (range 1–89 days). The most common reason for the discontinuation of steroids was death or deteriorating condition. Symptom scores improved at some stage for the majority of patients started on steroids for anorexia, nausea, pain, low mood, vomiting and weakness but not in patients complaining of dyspnoea or poor mobility. The most common side-effects that were most probably attributable to steroid therapy were oral candidosis and proximal myopathy. The benefits of steroids when used according to defined guidelines were thought to outweigh toxicity.

The use of the Edmonton Symptom Assessment Scale (ESAS) within a palliative care unit in the UK

The Edmonton Symptom Assessment scale (ESAS) was used on 1004 occasions to assess 71 patients with advanced malignant disease admitted to a palliative care unit in the UK over a six-week period. The median length of inpatient stay was eight days (range 1–36) and the median survival from start of ESAS to death was 16 days (range 2–202). Across all patients there was a trend towards worsening symptom scores over the first five days from admission with a significant deterioration in appetite scores. When scores were analysed retrospectively over five days according to outcome (death–group 1, or discharge–group 2) there was a significant improvement in pain scores in group 2 but no change in overall score, and a significant deterioration in activity, drowsiness and appetite in group 1 with no change in overall score. ESAS did not seem an appropriate tool in this group of patients as the total symptom scores were so often biased by the inevitable increase in individual symptom scores immediately prior to death.

Xerostomia in Patients with Advanced Cancer

The aim of the study was to investigate the features of xerostomia in patients with advanced cancer. The protocol involved completion of the Memorial Symptom Assessment Scale, and measurement of the unstimulated whole salivary flow rate (UWSFR) and the stimulated whole salivary flow rate (SWSFR). One hundred twenty patients participated in the study. Xerostomia was the fourth most common symptom (78% of patients). It was associated with a poor performance status (P = 0.01). The usual cause of xerostomia was drug treatment. There was an association with the total number of drugs prescribed (P = 0.009): the median number of xerostomic drugs prescribed was 4. Xerostomia was ranked the third most distressing symptom. Its severity was correlated with the severity of oral discomfort, dysgeusia, dysmasesia, dysphagia, dysphonia, and anorexia. The UWSFR was a relatively sensitive, but nonspecific, investigation. In contrast, the SWSFR was a relatively specific, but insensitive, investigation.

A Phase II Study to Establish the Efficacy and Toxicity of Sodium Valproate in Patients With Cancer-Related Neuropathic Pain

The efficacy and toxicity of sodium valproate for cancer-related neuropathic pain was evaluated in a phase II study at this cancer center. Twenty-five patients entered the study over a 13 month period. Pain was assessed using a pain scale based on the Brief Pain Inventory at days 0, 8 and 15. Nineteen patients completed the two week study period, one patient discontinued treatment because of toxicity, and five discontinued because of progressive disease. The most frequently observed side effects were drowsiness, unsteadiness, nausea, and decreased appetite. Response was defined as a decrease in pain score in the absence of increased need for analgesic medication. The response rate for average pain at day 15 in assessable patients was 55.6% (30.8-78.5%, 95% CI), but response rates varied considerably depending on the mode of analysis. Baseline efficacy data have been gained on which to base future comparative studies against antidepressants.

Experience in the use of the palliative care outcome scale

Goals of workThe objective of the study is to assess the Palliative Care Outcome Scale (POS) as a potential audit tool within a specialist cancer centre. It also aims to answer the following questions: does the tool identify problem areas and demonstrate changes in quality of life over time? How well do staff and patient ratings correlate?Patients and methodsThe POS questionnaire was piloted at a specialist cancer centre. Thirty consecutive patients admitted to the palliative care wards and ward staff completed questionnaires on admission and twice weekly until discharge or death. A further questionnaire assessed staff attitudes.ResultsThere was a significant improvement in overall patient POS score at 1 week (days 5–9). Four “symptoms” or issues were scored as being important for our patients: pain, other symptoms, anxiety and patient’s perception of family anxiety. These all significantly improved within the first week. At the initial assessment, staff underestimated patients’ pain and overestimated problems relating to information giving and patients’ ability to share their feelings. There was no significant difference between staff and patient scores after 1 week. The other six areas covered by the tool were less important; this may reflect the patient population seen at our centre. Use of the tool identified areas for staff training and effectively demonstrated improvement in patient care.ConclusionThe POS is an outcome measure tool designed to assess physical, psychological, practical and existential aspects of quality of life. It may be useful in identifying problems in individual patients and directing care to address these needs.

Salivary gland hypofunction in patients with advanced cancer

There is relatively little data on salivary gland hypofunction (SGH) in patients with advanced cancer. The aim of the current study was to investigate the epidemiology, aetiology, and clinical features of SGH in this group of patients. The protocol involved completion of standard proforma, completion of a Memorial Symptom Assessment Scale, measurement of unstimulated whole salivary flow rate (UWSFR), and measurement of stimulated whole salivary flow rate (SWSFR). One hundred and twenty patients participated in the study. Ninety-eight (82%) patients had an abnormally low UWSFR, whilst 50 (42%) patients had an abnormally low SWSFR. One hundred and seventeen (97.5%) patients were receiving prescribed medications that are known to cause SGH. There was an association between UWSFR and xerostomia, oral discomfort, dysphonia and dysphagia. Similarly, there was an association between SWSFR and xerostomia, oral discomfort, and dysphagia. In conclusion, the results of this study indicate that SGH is a common problem in patients with advanced cancer. Moreover, it often results in significant morbidity.

The role of embolization in palliative care

Transcatheter arterial embolization (TCAE) is a well recognized radiological technique that has been used for over 25 years. It is a method of diminishing blood flow through selected vessels by inserting haemostatic material under angiographic control. The procedure is performed under local anaesthetic through a femoral or, occasionally, an axillary approach. We present our experience of the use of TCAE in the management of pain and haemorrhage in three hospice inpatients in whom other options had been exhausted. The use of TCAE as a technique for the palliation of these symptoms in the hospice setting is discussed.

Is there a dose response relationship for clodronate in the treatment of tumour induced hypercalcaemia

Eighty-six patients with tumour induced hypercalcaemia were randomised to 600, 900, 1200 or 1500 mg of intravenous clodronate, according to post hydration serum calcium levels. Sixty-seven were evaluable for response. The overall response rate was 49.3% (95% CI: 36.8–61.8) with no significant difference in response rates, i.e. achievement of normocalcaemia at days 6–9 (corrected serum calcium ⩽2.6 mmol l−1) across all groups.