The management of constipation in palliative care: clinical practice recommendations.

Constipation is one of the most common problems in patients receiving palliative care and can cause extreme suffering and discomfort. The aims of this study are to raise awareness of constipation in palliative care, provide clear, practical guidance on management and encourage further research in the area. A pan-European working group of physicians and nurses with significant experience in the management of constipation in palliative care met to evaluate the published evidence and produce these clinical practice recommendations. Four potentially relevant publications were identified, highlighting a lack of clear, practical guidance on the assessment, diagnosis and management of constipation in palliative care patients. Given the limited data available, our recommendations are based on expert clinical opinion, relevant research findings from other settings and best practice from the countries represented. Palliative care patients are at a high risk of constipation, and while general principles of prevention should be followed, pharmacological treatment is often necessary. The combination of a softener and stimulant laxative is generally recommended, and the choice of laxatives should be made on an individual basis. The current evidence base is poor and further research is required on many aspects of the assessment, diagnosis and management of constipation in palliative care.

Analgesia for patients with advanced disease: 2.

The first article in this series explored epidemiology and patterns of pain in advanced disease, non-pharmacological treatments, and the use of opioids to manage pain. This second article examines the use of non-opioid drugs and anaesthetic interventions for pain relief in advanced disease. It also discusses an approach to managing analgesia in dying patients and finally looks at future developments.

Analgesia for patients with advanced disease: I.

This series of two articles explores the challenge of managing pain in patients with advanced malignant and non-malignant disease. Pain is a common symptom in advanced disease. Despite guidance from organisations such as the World Health Organisation, cancer pain is often inadequately managed. Managing pain in non-malignant conditions, such as end stage cardiac failure, presents an even greater challenge to healthcare professionals. This first article discusses epidemiology, definitions, pathophysiology, assessment, non-pharmacological approaches, the analgesic "ladder", and opioids. The second article will examine the use of non-opioids, anaesthetic techniques, and analgesia in dying patients as well as discussing future directions.

The relationship between opioid use and laxative use in terminally ill cancer patients.

The frequency of the use of laxatives, and the relationship between doses of laxatives and of opioid analgesia, were determined by a prospective study of 498 hospice inpatients with advanced cancer. Laxatives were required by 87% of patients taking oral strong opioids, 74% of those on weak opioids and 64% of those not receiving opioid analgesia. The form of the relationship appears to be hyperbolic, as suggested by the presentation of the results arranged by opioid quartile and by the improved correlation obtained by subjecting the opioid data to a logarithmic transformation. It is concluded that opioids account for about a quarter of the constipation found in terminally ill cancer patients in a hospice. However, the dose of laxative required is likely to be significantly higher if an opioid is being taken than if not. The form of the relationship between laxative and strong opioid doses is what might be expected from the mediation of opioid-induced constipation by opioid receptors.

A volunteer model for the comparison of laxatives in opioid-related constipation.

Loperamide was used to provide a source of opioid-induced constipation in healthy volunteers. Each volunteer took a sequence of three dose levels of loperamide. One of three laxatives was used to counterbalance the effect of loperamide and restore bowel function to what the individual considered normal at each stage before the dose of loperamide was increased. Lactulose, senna, and codanthrusate were selected as examples of a softening, a stimulant, and a combination laxative, respectively. Outcome measures were the doses of laxative used, stool form and frequency, ease of defecation, a rating scale of subjective bowel function, and the occurrence of adverse effects. Each laxative was taken by ten volunteers, and all proved capable of maintaining normal bowel function. A combination of stimulant and softening laxatives was most likely to maintain normal bowel function at the lowest dose and least adverse effects. The mean final dose of lactulose was excessive for use in ill patients. Senna was associated with significantly more adverse effects than the other laxatives, mainly abdominal pain (P < 0.001). This model of constipation may provide a standardized means of assaying the clinical effectiveness of oral laxatives.

An investigation of the ability of oral naloxone to correct opioid-related constipation in patients with advanced cancer.

A dose-ranging study of the use of oral naloxone in opioid-related constipation in patients with far-advanced cancer is reported. Naloxone doses were calculated as a percentage of the morphine dose each patient was receiving. Seventeen patients entered the first phase of the study, which had a randomised, double-blind design. Outcome measures were small bowel transit time (SBTT) measured by the lactulose/hydrogen breath test, pain scores and the occurrence of adverse events. One subject was excluded before receiving naloxone. No significant difference between placebo and naloxone occurred in the 14 remaining patients receiving total daily doses of naloxone 10% or less of the 24 h dose of morphine. Two further patients experienced a marked laxative effect with naloxone at 20% of the 24 h dose of morphine. In one of these, SBTT was available and was unchanged from placebo. The other declined to continue with SBTT measurement. Phase two of the study had an open design, in which laxative effects were determined clinically. Naloxone at a maximum dose level of 20% was given to seven patients, up to 40% to two patients and up to 80% to one patient. Four out of the seven patients in the 20% dose level group, and all of the remainder, experienced laxative effects. Two patients experienced symptoms of opioid withdrawal, one of whom also had return of pain. It is concluded that oral naloxone at a daily dose of 20% or more of the prevailing 24 h morphine dose is a potentially valuable therapy for opioid-related constipation. However, opioid withdrawal was observed and it is suggested that initial individual naloxone doses should not exceed 5 mg. Further research is needed into the oral absorption of naloxone, as well as further studies of clinical efficacy and dosing.

Current approaches to the management of constipation.

Constipation in patients with advanced cancer results from reduced food intake and debility as well as medication, particularly opioid analgesics. Prophylactic measures are important, but most patients will require laxatives. History and examination should exclude the presence of intestinal obstruction, and if there is doubt, only a softening laxative should be used. In general, a combination of softening and stimulant laxatives is most likely to be successful with minimum adverse effects. Management of constipation is frequently poor, and considerable research effort is needed into both the more effective use of current treatments and the development of new therapies.

Use of chloramphenicol in a hospice.

Chloramphenicol has been the antibiotic of first choice at St Christopher's Hospice for over 20 years. Its use has been justified on the grounds of efficacy and tolerability in a patient group with a short prognosis in whom good symptom control is the priority. The sensitivities of hospice bacterial cultures to chloramphenicol and other antibiotics were recorded and were compared with the chloramphenicol sensitivities of cultures obtained from a series of hospital patients in the same area. Assessment of the occurrence of side effects attributed to chloramphenicol was made from hospice casenotes. Chloramphenicol was widely effective, but there was some evidence of the emergence of resistant strains, particularly of coliforms. Side effects were encountered less frequently than might have been expected from the use of popular alternative oral antibiotic drugs.

Clinical and pathological study of dysphagia conservatively managed in patients with advanced malignant disease.

A series of patients with dysphagia associated with terminal malignant disease is presented. 33 patients had clinical evidence of organic dysphagia associated with tumours of the upper aerodigestive tract. Over 80% of this group who underwent necropsy had locally obstructive lesions. Conservative treatment alone led to amelioration of dysphagia in approximately 60% of patients.

Pain control in terminal cancer.

It is possible to totally relieve pain in patients with terminal cancer in 85% of cases, and significantly modify pain in a further 10%. This requires the proper use of analgesics of which oral morphine is the most frequently used. Specific adjuvant therapies, which include radiotherapy and surgery as well as drugs, are also important. Optimal pain relief depends on assessment of the wider aspects of 'total pain', full support of the patient and their family, and good communication.