Palliative Sedation Therapy Does Not Hasten Death

July 7, 2009 – Palliative sedation therapy used for the control of refractory symptoms in cancer patients with very advanced disease does not hasten death, a new prospective study concludes.

The study is reported in the July issue of the Annals of Oncology and is described as an "important contribution" to the field in an accompanying editorial.

When palliative sedation therapy is used to relieve refractory distress at the end of life, the question of whether it hastens death is a significant one, say the researchers. This is a concern for both oncologists and palliative specialists administering the treatment, as well as for the patients and/or the relatives who agree to it.

The concern is that this therapy could be a disguised form of euthanasia because death often comes fairly rapidly after sedation, the researchers comment.

"I think that many physicians think that palliative sedation therapy is or could be a form of 'slow' or 'soft' euthanasia,' " lead author Marco Marco Maltoni, MD, director of the Valerio Grassi Hospice, in Forlimpopoli, Italy, commented to Medscape Oncology. 

But the results of this new study show that the therapy does not have a detrimental effect on survival, and they should be reassuring, he commented. "I would say that our results may help physicians and patients who do not accept euthanasia to have a good clinical practice, so that no patient is forced to reach death in a symptomatic way."

First Trial to Match Patients Prospectively 

There have been previous trials showing that palliative sedation therapy does not accelerate the demise of the patients, but they have been criticized for methodology. "These data were indicative but not conclusive, insofar as there was a possibility that the patient populations were intrinsically different, with different prognoses and different anticipated trajectories of demise," notes the editorialist Nathan Cherny, MD, head of the palliative medicine unit at the Shaare Zedek Medical Center, in Jerusalem, Israel.

This latest trial is the first — as far as the authors are aware — that prospectively matched sedated patients with nonsedated patients in such a way that the 2 cohorts differed only in terms of 1 characteristic (ie, sedation).

Dr. Maltoni and colleagues recruited 518 patients from 4 hospices in the Emilia-Romagna region of Italy. The overall prevalence of palliative sedation therapy in the patients who were admitted to these hospices was 25.1%, with very little variability among the centers (+5%).

Patients in the 2 cohorts were matched for age, sex, Karnofsky performance status, reason for hospice admission, and predicted survival. In addition, there were no statistically significant differences in the location of the primary tumor or metastases. The most common cancers were lung, colorectal, stomach, breast, and pancreas, and the most common metastases were in the liver, lymph nodes, and bone.

Drugs used for palliative sedation included neuroleptics (used in 84.2% of patients) such as chlorpromazine, promethazine, and haloperidol, benzodiazepines (54.3%) such as lorazepam, midazolam, and diazepam, and opioids (25.5%) such as morphine.

Delirium and/or agitation were cited the most often as reasons for this therapy (in 78.7% of patients), followed by dyspnea (in 19.5% of patients), pain (in 11.2%), and vomiting (in 4.5%). Refractory psychological distress was cited in 18.7% of patients, but the majority of this group (37 of 50 patients) also presented with physical refractory symptoms, the researchers comment.

The mean duration of sedation was 4 days, while the median duration of sedation was 2 days (range, 0 – 43 days).
Overall survival was not statistically significant different in the 2 cohorts. The median survival of patients in the sedated group was 12 days, while that of unsedated patients was 9 days (P = .33; unadjusted hazard ratio, 0.92; adjusted hazard ratio, 0.86). The overall survival curves of the 2 cohorts were superimposable, the researchers commented.

"Palliative sedation therapy does not shorten life when used to relieve refractory symptoms," the researchers conclude.

Important and Necessary Therapy 

This study shows that, even when matched for adverse prognostic variables, sedated patients in this setting did not have an accelerated demise, notes Dr. Cherny.

However, he says, it is important to note that the majority of patients in this study were lightly sedated. The same may not apply to sudden deep sedation.

Another issue that is unresolved is whether or not to continue hydration in patients who are sedated. This question was not evaluated in the current trial, Dr. Cherny points out.

But the researchers comment that "even if hydration had been interrupted in a higher number of sedated patients with respect to the nonsedated group, this would, at most, have had a detrimental effect on the former cohort . . . [but] this effect was not observed."

"For oncologists and palliative care specialists, sedation is an important and necessary therapy in the care of selected patients with otherwise refractory and severe distress at the end of life," Dr. Cherny writes in the editorial.
However, he adds that as "sedation has the capacity to harm as well as to help, the manner in which this therapeutic tool is applied is important."

A number of procedural guidelines for the use of sedation in the management of palliative care have already been published, and a framework for developing such guidelines is currently being developed by the European Association for Palliative Care, he notes.

No Need for Doctrine of Double Effect 

These latest results confirm findings from previous studies of a lack of effect of palliative sedation therapy on survival, the researchers comment. Hence, it does not need the "doctrine of double effect" to justify its use from an ethical point of view, they add.

Dr. Maltoni explained to that this doctrine of double effect is a bioethical principle. "This doctrine says that if doing something morally good has a morally bad adverse effect, it is ethically acceptable to do it provided the bad effect was not intended. This is true even if it is foreseen that the bad effect would probably happen."

In the case of palliative sedation therapy, a previous study has suggested around 3% to 4% of patients may have a serious adverse event, even death. But as the treatment is beneficial, and this adverse event is not wanted and not predictable in an individual patient, the therapy "is ethically acceptable from any point of view and ethical perspective," Dr. Maltoni told Medscape Oncology.

"Unfortunately, serious adverse effects are frequent in all medical acts, but they cannot stop appropriate care and therapies," he added.

No conflicts of interest were reported. 

Ann Oncol. 2009;20:1163-1169 Abstract, 1153-1155. Abstract