Title: The impact of morphine fentanyl or codeine (oxycodone) on patient consciousness appetite and thirst
Funder: Department of Health (England)

Abstract: BackgroundThere is increasing focus on providing high quality care for people at the end of life irrespective of disease or cause and in all settings. In the last ten years the use of care pathways to aid those treating patients at the end of life has become common worldwide. The use of the Liverpool Care Pathway in the UK has been criticised. In England the LCP was the subject of an independent review commissioned by a Health Minister. The Neuberger Review acknowledged that the LCP was based on the sound ethical principles that provide the basis of good quality care for patients and families when implemented properly. It also found that the LCP often was not implemented properly and had instead become a barrier to good care; it made over 40 recommendations including education and training research and development access to specialist palliative care services and the need to ensure care and compassion for all dying patients. In July 2013 the Department of Health released a statement that stated the use of the LCP should be phased out over the next 6-12 months and replaced with an individual approach to end of life care for each patient.The impact of opioids was a particular concern because of their potential influence on consciousness appetite and thirst in people near the end of life. There was concern that impaired patient consciousness may lead to an earlier death and that effects of opioids on appetite and thirst may result in unnecessary suffering. This rapid review commissioned by the National Institute for Health Research used standard Cochrane methodology to examine adverse effects of morphine fentanyl oxycodone and codeine in cancer pain studies as a close approximation to possible effects in the dying patient.ObjectivesTo determine the impact of opioid treatment on patient consciousness appetite and thirst in randomised controlled trials of morphine fentanyl oxycodone or codeine for treating cancer pain.Search methodsWe assessed adverse event data reported in studies included in current Cochrane reviews of opioids for cancer pain: specifically morphine fentanyl oxycodone and codeine.Selection criteriaWe included randomised studies using multiple doses of four opioid drugs (morphine fentanyl oxycodone and codeine) in cancer pain. These were taken from four existing or on going Cochrane reviews. Participants were adults aged 18 and over. We included only full journal publication articles.Data collection and analysisTwo review authors independently extracted adverse event data and examined issues of study quality. The primary outcomes sought were numbers of participants experiencing adverse events of reduced consciousness appetite and thirst. Secondary outcomes were possible surrogate measures of the primary outcomes: delirium dizziness hallucinations mood change and somnolence relating to patient consciousness and nausea vomiting constipation diarrhoea dyspepsia dysphagia anorexia asthenia dehydration or dry mouth relating to appetite or thirst. Comparative measures of harm were known to be unlikely and we therefore calculated the proportion of participants experiencing each of the adverse events of interest with each opioid and for all four opioid drugs combined.Main resultsWe included 77 studies with 5619 randomised participants. There was potential bias in most studies with small size being the most common; individual treatment groups had fewer than 50 participants in 60 studies. Participants were relatively young with mean age in the studies typically between 50 and 70 years. Multiple major problems with adverse event reporting were found including failing to report adverse events in all participants who received medication all adverse events experienced how adverse events were collected and not defining adverse event terminology or whether a reporting system was used.Direct measures of patient consciousness patient appetite or thirst were not apparent. For opioids used to treat cancer pain adverse event incidence rates were 25% for constipation 23% for somnolence 21% for nausea 17% for dry mouth and 13% for vomiting anorexia and dizziness. Asthenia diarrhoea insomnia mood change hallucinations and dehydration occurred at incidence rates of 5% and below.Authors conclusionsWe found no direct evidence that opioids affected patient consciousness appetite or thirst when used to treat cancer pain. However somnolence dry mouth and anorexia were common adverse events in people with cancer pain treated with morphine fentanyl oxycodone or codeine.We are aware that there is an important literature concerning the problems that exist with adverse event measurement reporting and attribution. Together with the known complications concerning concomitant medication data collection and reporting and nomenclature this means that these adverse events cannot always be attributed unequivocally to the use of opioids and so they provide only a broad picture of adverse events with opioids in cancer pain. The research agenda includes developing definitions for adverse events that have a spectrum of severity or importance and the development of appropriate measurement tools for recording such events to aid clinical practice and clinical research.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: GENERIC HEALTH RELEVANCE