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Palliative sedation therapy is frequently used in end of life in various
settings to relief pain and sufferings in terminally ill patients.
Poorly controlled pain causes significant
distress and disability and therefore,
the effective management of pain
is an essential element of palliative
Drug classes used for palliative sedation
include benzodiazepines (particularly
midazolam and clonazepam),
antipsychotics, opioids, and hypnotics.
They may be administered either
intravenously or subcutaneously.
The therapy usually varies in terms of level
of sedation (mild, intermediate and deep),
and duration (intermittent or continuous).3
To date, results conflict with regards to
the effectiveness of the pharmacological
management used to sedate terminally
ill people, in the terminal phase of life,
separate from the broader palliative
The studies included in this review
were Randomised controlled trials
(RCTs), quasi-RCTs, non-RCTs, and
observational studies (e.g. before-and-
after, interrupted-time series) with
quantitative outcomes. The types of the
studies were varied due to the sensitive
nature of the research question and the
ethical dilemmas associated with it.
Quality of the research
Studies included in the report were of
poor methodological quality. Biases such
potential selection bias and reporting
of confounding factors were the major
The following databases were searched
Cochrane Central Register of Controlled
Trials (CENTRAL; 2014, Issue 11),
MEDLINE (1946 to Nov 2014), and
EMBASE (1974 to Dec 2014), using search
terms representing the sedative drug
names and classes, disease stage, and
The review included a total of
14 studies, involving 4,167 adults, of
whom 1,137 received palliative sedation.
The majority of the participants (95%)
were diagnosed with a type of cancer.
There were no randomised or quasi-
randomised studies included. All were
consecutive case series, with only three
having prospective data collection due to
the ethical nature of the research question.
None of the studies measured quality of
life or participant well-being. Only five
studies measured symptom control,
using four different methods, so a
meta-analysis was not appropriate.
The primary outcome measured was
quality of life or well-being and the
secondary outcomes included symptom
control and adverse events.
No studies reported on the reviews
primary outcome. Symptom control was
measured in five studies using various
methods and therefore none of the
results could be pulled together.
Overall, control of symptoms was
suboptimum despite sedation. Delirium
and dyspnoea were still troublesome
symptoms in these people in the last few
days of life, and were significantly worse
in the sedated group. Control of other
symptoms appeared to be similar in
sedated and non-sedated groups.
Only one study reported on survival
rates and showed that sedation had no
impact on survival rates in both groups
of patients (sedated and non-sedated).
This is an important finding as it negates
Dr Hanan Khalil is the Director of the Centre for
Chronic Disease Management, a collaborating centre
of the Joanna Briggs Institute, Faculty of Medicine,
Nursing and Health Sciences, Monash University, and
a reviewer for the consumer group of the Cochrane
Collaboration. Hanan is also the Editor in Chief of the
International Journal of Evidenced Based Health Care.
The purpose of this evidence summary is to provide
the best available evidence for managing sedation
for terminally ill patients. For the full review, refer to
the thought of sedation is a form of
euthanasia and ending life.
There was no statistically significant
difference between the sedated and
non-sedated groups in the prevalence
of adverse events such as confusion,
gastrointestinal symptoms, pain, or
psychological distress. The odds ratio
for recurrent agitation was 3.5 (95%CI
1.4 to 8.8), for recurrent drowsiness was
0.3 (95% CI 0.2 to 0.7), and for recurrent
dyspnoea was 4.2 (95%CI 1.9 to 9.2),
indicating that the sedated group was
more likely to experience recurrent
agitation and dyspnoea, but less likely to
experience recurrent drowsiness than the
Implications for research and
Only a few studies met the inclusion
criteria of the research question. No single
study measured the patients' quality of life
or well-being in sedated patients.
The current evidence suggests that
sedation does not control diseases
symptoms in terminally ill patients. It was
also found that sedation does not hasten
death. Moreover, patients taking sedatives
were more likely to experience agitation
and dyspnoea than non-sedated patients.
1. Beller EM, van Driel ML, McGregor L, Truong S, Mitchell G.
Palliative pharmacological sedation for terminally ill adults.
Cochrane Database of Systematic Reviews 2015, Issue 1. Art.
No.: CD010206. DOI: 10.1002/14651858.CD010206.pub
2. Kohara H, Ueoka H, Takeyama H, Murakami T, Morita
T. Sedation for terminally ill patients with cancer with
uncontrollable physical distress. Journal of Palliative Medicine
3. De Graeff A, Dean M. Palliative sedation therapy in the last
weeks of life: a literature review and recommendations for
standards. Journal of palliative medicine 10.1 (2007): 67--85.
4. Portnoy, Aron, et al. The Use of Palliative Sedation to Treat
Existential Suffering: A Reconsideration. Sedation at the End-
of-life: An Interdisciplinary Approach. Springer Netherlands,
BY DR HANAN KHALIL
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