Elsevier

The Lancet Oncology

Volume 4, Issue 5, May 2003, Pages 312-318
The Lancet Oncology

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The use of opioids and sedatives at the end of life

https://doi.org/10.1016/S1470-2045(03)01079-9Get rights and content

Summary

Opioids and sedative drugs are commonly used to control symptoms in patients with advanced cancer. However, it is often assumed that the use of these drugs inevitably results in shortening of life. Ethically, this outcome is excused by reference to the doctrine of double effect. In this review, we assess the evidence for patterns of use of opioids and sedatives in palliative care and examine whether the doctrine of double effect is needed to justify their use. We conclude that patients are more likely to receive higher doses of both opioids and sedatives as they get closer to death. However, there is no evidence that initiation of treatment, or increases in dose of opioids or sedatives, is associated with precipitation of death. Thus, we conclude that the doctrine of double effect is not essential for justification of the use of these drugs, and may act as a deterrent to the provision of good symptom control.

Section snippets

Opioids

We identified 17 studies which examined the use of opioids at the end of life,8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 and analysed them for patterns of opioid use, types of opioid used, mean doses, and effect of opioid use on survival.

The use of opioids in palliative care

Opioids are commonly used in palliative care for the treatment of pain,25 dyspnoea,26 and cough (figure 2). Higher doses of opioids are required in some clinical situations such as neuropathic pain, advancing disease, metabolic variation, and in younger patients.27 Such factors may explain some interindividual variation in the effectiveness of opioids, but the use of adjuvant analgesics and attention to non-physical factors, which may be exacerbating pain, need to be considered alongside dose

Frequency

The reported frequency of opioid use in the last few days of life varies from 25% to 99%.14, 18 Generally, patients receiving community palliative care seem to be given less opioids. Goldberg and colleagues reported that 66% of patients being cared for at home received opioids compared with 78% of hospice patients.19 Patients receiving conventional care (ie, care without specialist palliation) received less opioids than either of the other two groups, possibly confirming the presence of

Effect on survival

Five studies have looked at the effect of opioid use on survival, although they used different methods.8, 9, 10, 12, 32 None of the studies reported that opioids had shortened life. However, this aspect does not seem to have been as frequently examined with opioids as it has been with sedatives.

Bercovitch and colleagues found no difference in survival between patients receiving high doses and those receiving low doses.8 Furthermore, there were no cases of respiratory depression. Morita and

Guidelines for opioid use at the end of life

Guidelines on the use of opioids in palliative care advocate the careful titration of opioid according to the patient's pain. They also offer reassurance that the appropriate use of morphine should not shorten life and that there is no reason to withhold opioids in the last few days.34, 35

The evidence we report in this review supports these guidelines. Although studies generally report a gradual increase in opioid dose up until the end of life, there is no apparent shortening of life when

Sedation

We identified 17 studies (including 2 yet to be published by Morita and colleagues, and Scholes and colleagues, respectively) that addressed the use of sedatives in the care of cancer patients in the final stages of life.10, 14, 22, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47 In addition, we included a systematic review that analysed three studies published in Spanish.48

Patterns of sedative use

Table 4 shows the frequency and length of sedative use in various studies and table 5 describes the types of drug and indications for sedation. The prevalence of sedation varies widely, from 1% to 88% among the populations analysed. This variation is partly due to differences in definitions of sedation. Studies reporting a proportional use of sedation show a mean use of 45%, whereas the small number of studies using so-called “sudden” sedation report a mean use of 16%. It is fair to expect that

Effect of sedation on survival

The most important ethical question is whether the use of sedatives shortens the life of terminally ill patients. A definitive answer to this question could only be obtained from a randomised controlled trial in which patients were randomly allocated to sedation or non-sedation groups. But this solution is ethically impossible.

Ten studies have estimated the average duration for which sedation was used (table 4). The weighted mean duration from these studies is 2·8 days, a figure that could

Conclusion

Sedatives are used commonly in patients with cancer at the end of life. In most cases they are not given with the intention of inducing sleep. Instead, the dose is titrated against the relief of a specific symptom, most often an agitated delirium, to the point where the symptom is adequately relieved. The impairment of consciousness is not an objective but an accompaniment to the use of the medication, and varies in its extent.

Sedation is generally used over a short period and most of the

Guidance

Cherny and Portenoy have produced guidelines for the use of sedatives for symptom control.1 Sedation should be used appropriately for specified symptoms once therapeutic alternatives have been considered and found ineffective or inapplicable to the present situation. As agents of symptom control, not of life shortening, sedative drugs should be given in doses that are titrated against the response to balance relief of symptoms with the distress they cause.

Benzodiazepines are the most favoured

The doctrine of double effect

The doctrine of double effect is used as an ethical justification for the specific risk of foreseeable life shortening as a result of a medical treatment. However, we suggest that there is no evidence that the use of opioids or sedatives in palliative care requires the doctrine of double effect as a defence. We have specifically examined the role of this doctrine in relation to symptom control and found that in 238 patients in a specialist palliative-care unit (89% receiving strong opioids and

Search strategy and selection criteria

Searches of Medline, Embase, CancerLit, CINAHL, and Cochrane databases were done with the search terms “palliative care”, “hospice”, “cancer”, “opioids”, “sedatives”, “euthanasia”, “ethics”, and “double effect”. Manual searches of reference lists of articles were also done. The Halley Stewart Library at St Christopher's Hospice was also searched. Papers were limited to detailed retrospective or prospective studies of the use of opioids or sedatives or both in the palliative care of cancer

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