Sedation medication for relieving symptoms at the end of life

Background

People with diseases that are not curable may have a variety of symptoms at the end of life. These symptoms can include confusion (delirium), anxiety, restlessness, breathlessness (dyspnoea), pain, vomiting, and distress. Medicines that reduce consciousness (sedatives) may help relieve these symptoms when people are close to death.

Treatment with sedatives can vary in terms of the level of sedation (mild, intermediate, and deep), and duration (intermittent or continuous).

Study chara cteristics

We searched international databases in October 2012 and again in December 2014 for studies of terminally ill adults who required sedation in order to control symptoms. We found 14 studies of around 4000 people. The studies compared sedation versus non-sedation. Most people in the studies had cancer (95%). The studies took place in hospices, palliative care units, hospitals, and the home.

Key results

Five studies showed that sedatives did not fully relieve delirium or breathlessness. There was no difference between the groups in terms of the other symptoms. There was no difference in time from admission or referral to death

Only one study reported side effects, and did not report any major problems.

Future studies should focus on how sedatives affect a person's quality of life, or peacefulness and comfort during the dying phase, and how well sedation controls the distressing symptoms. Side effects should be better reported.

Quality of evidence

The studies were not randomised controlled trials (where people are randomly allocated to one of two or more treatment groups), and so we judged the quality of the evidence as poor.

Authors' conclusions: 

There was insufficient evidence about the efficacy of palliative sedation in terms of a person's quality of life or symptom control. There was evidence that palliative sedation did not hasten death, which has been a concern of physicians and families in prescribing this treatment. However, this evidence comes from low quality studies, so should be interpreted with caution. Further studies that specifically measure the efficacy and quality of life in sedated people, compared with non-sedated people, and quantify adverse effects are required.

Read the full abstract...
Background: 

Terminally ill people experience a variety of symptoms in the last hours and days of life, including delirium, agitation, anxiety, terminal restlessness, dyspnoea, pain, vomiting, and psychological and physical distress. In the terminal phase of life, these symptoms may become refractory, and unable to be controlled by supportive and palliative therapies specifically targeted to these symptoms. Palliative sedation therapy is one potential solution to providing relief from these refractory symptoms. Sedation in terminally ill people is intended to provide relief from refractory symptoms that are not controlled by other methods. Sedative drugs such as benzodiazepines are titrated to achieve the desired level of sedation; the level of sedation can be easily maintained and the effect is reversible.

Objectives: 

To assess the evidence for the benefit of palliative pharmacological sedation on quality of life, survival, and specific refractory symptoms in terminally ill adults during their last few days of life.

Search strategy: 

We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 11), MEDLINE (1946 to November 2014), and EMBASE (1974 to December 2014), using search terms representing the sedative drug names and classes, disease stage, and study designs.

Selection criteria: 

We included randomised controlled trials (RCTs), quasi-RCTs, non-RCTs, and observational studies (e.g. before-and-after, interrupted-time-series) with quantitative outcomes. We excluded studies with only qualitative outcomes or that had no comparison (i.e. no control group or no within-group comparison) (e.g. single arm case series).

Data collection and analysis: 

Two review authors independently screened titles and abstracts of citations, and full text of potentially eligible studies. Two review authors independently carried out data extraction using standard data extraction forms. A third review author acted as arbiter for both stages. We carried out no meta-analyses due to insufficient data for pooling on any outcome; therefore, we reported outcomes narratively.

Main results: 

The searches resulted in 14 included studies, involving 4167 adults, of whom 1137 received palliative sedation. More than 95% of people had cancer. No studies were randomised or quasi-randomised. All were consecutive case series, with only three having prospective data collection. Risk of bias was high, due to lack of randomisation. No studies measured quality of life or participant well-being, which was the primary outcome of the review. Five studies measured symptom control, using four different methods, so pooling was not possible. The results demonstrated that despite sedation, delirium and dyspnoea were still troublesome symptoms in these people in the last few days of life. Control of other symptoms appeared to be similar in sedated and non-sedated people. Only one study measured unintended adverse effects of sedative drugs and found no major events; however, four of 70 participants appeared to have drug-induced delirium. The study noticed no respiratory suppression. Thirteen of the 14 studies measured survival time from admission or referral to death, and all demonstrated no statistically significant difference between sedated and non-sedated groups.

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