Cochrane Database Syst Rev. 2015 Jan 2;1:

Palliative pharmacological sedation for terminally ill adults.

Beller EM1, van Driel ML, McGregor L, Truong S, Mitchell G.

Author information

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 sedationtherapy 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 ofsedation; 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 METHODS:

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.

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.

PMID:

 

25879099

 

[PubMed - in process]

J Pain Symptom Manage. 2009 May;37(5):771-9Nov 28.

Controlled sedation for refractory symptoms in dying patients.

Mercadante S1, Intravaia G, Villari P, Ferrera P, David F, Casuccio A.

Author information

Abstract

Terminally ill cancer patients near the end of life may experience intolerable suffering refractory to palliative treatment. Although sedation is considered to be an effective treatment when aggressive efforts fail to provide relief in terminally ill patients, it remains controversial. The aim of this study was to assess the need and effectiveness of sedation in dying patients with intractable symptoms, and the thoughts of relatives regardingsedation. A prospective cohort study was performed on a consecutive sample of dying patients admitted to an acute pain relief and palliative care unit within a cancer center. Indications for sedation, opioid and midazolam doses, level of delirium and sedation, nutrition, hydration, rattle, inability to cough and swallow, pharyngeal aspiration, duration of sedation and survival, and use of anticholinergics or other drugs were recorded. Family members were interviewed. Forty-two of 77 dying patients were sedated, and had a longer survival than those who were not sedated (P=0.003). 

Prevalent indications for sedation were dyspnea and/or delirium. Twelve patients began with an intermediate sedation, and 38 patients started with definitive sedation. The median sedation duration was 22 hours. Opioid doses did not change during sedation. Agitated delirium significantly decreased with increasing doses of midazolam, whereas the capacity to communicate concomitantly decreased. Interviewed relatives were actively involved in the process of end-of-life care, and the decision to sedate, and the efficacy of sedation, were considered appropriate by almost all relatives. 

Controlled sedation is successful in dying patients with untreatable symptoms, did not hasten death, and yielded satisfactory results for relatives. This study also points to the importance of palliative care and the experience of professionals skilled in both symptom control and end-of-life care.

PMID:

 

19041216

 

[PubMed - indexed for MEDLINE]

J Clin Oncol. 2012 Apr 20;30(12):1378-83. 

Palliative sedation in end-of-life care and survival:            a systematic review.

Maltoni M1, Scarpi E, Rosati M, Derni S, Fabbri L, Martini F, Amadori D, Nanni O.

Author information

Erratum in

• J Clin Oncol. 2012 Sep 20;30(27):3429.

Abstract

PURPOSE:

Palliative sedation is a clinical procedure aimed at relieving refractory symptoms in patients with advanced cancer. It has been suggested that sedative drugs may shorten life, but few studies exist comparing the survival of sedated and nonsedated patients. We present a systematic review of literature on the clinical practice of palliative sedation to assess the effect, if any, on survival.

METHODS:

A systematic review of literature published between January 1980 and December 2010 was performed using MEDLINE and EMBASE databases. Search terms included palliative sedation, terminal sedation, refractory symptoms, cancer, neoplasm, palliative care, terminally ill, end-of-life care, and survival. A manual search of the bibliographies of electronically identified articles was also performed.

RESULTS:

Eleven published articles were identified describing 1,807 consecutive patients in 10 retrospective or prospective nonrandomized studies, 621 (34.4%) of whom were sedated. One case-control study was excluded from prevalence analysis. The most frequent reason for sedation was delirium in the terminal stages of illness (median, 57.1%; range, 13.8% to 91.3%). Benzodiazepines were the most common drug category prescribed. Comparing survival of sedated and nonsedated patients, the sedation approach was not shown to be associated with worse survival.

CONCLUSION:

Even if there is no direct evidence from randomized clinical trials, palliative sedation, when appropriately indicated and correctly used to relieve unbearable suffering, does not seem to have any detrimental effect on survival of patients with terminal cancer. In this setting,palliative sedation is a medical intervention that must be considered as part of a continuum of palliative care.

Comment in

• Palliative sedation: when and how? [J Clin Oncol. 2012]
• Palliative sedation: further evidence needs to be accompanied by ethical guidance to ensure professional practice at the end of life. [J Clin Oncol. 2012]

PMID:

 

22412129

 

[PubMed - indexed for MEDLINE]

BMC Palliat Care. 2015 Mar 15;14:5.

Palliative sedation for terminally ill cancer patients in a tertiary cancer center in Shanghai, China.

Gu X1, Cheng W1, Chen M1, Liu M1, Zhang Z1.

Abstract

BACKGROUND:

There are a number of studies dedicated to characteristics of sedation, but these studies are mostly bound to western country practices. The aim of this study is to describe the characteristics of patients who suffered from cancer and who had been sedated until their death in Shanghai, China.

METHODS:

Retrospective medical data of 244 terminally ill cancer patients including 82 sedated patients were collected. Data collected included demographic characteristics, disease-related characteristics and details of the sedation.

RESULTS:

In sedated cases, patients and/or caregivers gave the consent to start palliative sedation due to unmanageable symptoms. On average,sedation was performed 24.65(±1.78)hours before death. Agitated delirium and dyspnea were the most frequent indications for palliative sedation. There was no significant difference in survival time from admission till death between sedated and non-sedated patients (p > 0.05).

CONCLUSIONS:

Palliative sedation is effective for reducing terminally ill cancer patients' suffering without hastening death. Prospective research is needed to determine the optimal conditions for Chinese patients including indications, decision making process, informed consent, cultural and ethical issues, type of sedation and drugs.

KEYWORDS:

Agitated delirium; End of life; Palliative sedation; Survival; Symptom management; Terminally ill cancer patients

PMID:

 

25810691

 

[PubMed] 

PMCID:

 

PMC4373517

 

Free PMC Article

Am J Hosp Palliat Care. 2015 Aug 13. 

A Distress Protocol for Respiratory Emergencies in Terminally Ill Patients With Lung Cancer or Chronic Obstructive Pulmonary Disease.

Godbout K1, Tremblay L1, Lacasse Y2.

Abstract

A combination of opioid, midazolam, and scopolamine (that we call "distress protocol" [DP]) is used to induce transient sedation when emergencies occur in palliative care.

 We wished to describe the prescription and administration of DP in terminally ill patients with either lung cancer or chronic obstructive pulmonary disease (COPD).

 In a retrospective study, 96 of 100 patients with cancer and 85 of 100 patients with COPD had a DP prescribed.

 Thirty patients with cancer and 29 with COPD received at least 1 DP.

 All patients receiving a DP for an appropriate indication were sedated within 30 minutes.

 There was no difference in survival from DP administration among patients who received it and those who did not.

© The Author(s) 2015.

KEYWORDS:

COPD; distress protocol; end-of-life symptoms; lung cancer; palliative crises

PMID:

 

26273094

 

[PubMed - as supplied by publisher]

Am J Hosp Palliat Care. 2015 Aug 13

A Distress Protocol for Respiratory Emergencies in Terminally Ill Patients With Lung Cancer or Chronic Obstructive Pulmonary Disease.

Godbout K1, Tremblay L1, Lacasse Y2.

Author information

Abstract

A combination of opioid, midazolam, and scopolamine (that we call "distress protocol" [DP]) is used to induce

 transient sedation when emergencies occur in palliative care.

 We wished to describe the prescription and administration of DP in terminally ill patients with either lung cancer or chronic obstructive pulmonary disease (COPD). 

In a retrospective study, 96 of 100 patients with cancer and 85 of 100 patients with COPD had a DP prescribed. Thirty patients with cancer and 29 with COPD received at least 1 DP. 

All patients receiving a DP for an appropriate indication were sedated within 30 minutes. There was no difference in survival from DP administration among patients who received it and those who did not.

© The Author(s) 2015.