To the editor:

We greatly appreciate the debate on the use of sedatives in palliative care and welcome the perspective of Dr. Twycross. In our response, we would like to add some comments from a research perspective. First, we strongly agree with Dr. Twycross that a shared worldwide definition and concept of sedation is of marked importance to make valid comparisons of the practice of sedation between countries, and evaluate the practice.1 Dr. Twycross’s examples suggest, in our view, not so much that continuous deep sedation is frequently ‘‘abused’’, but that different definitions could lead to different research results. For instance, the use of a definition of sedation that mixes descriptive language with criteria of due care will result in a smaller set of described sedation cases that willdas per the definitiondfulfill the criteria of due care. In contrast, the use of a descriptive definition such as ‘‘continuous deep sedation’’ will probably result in a larger set of described sedation cases, and will not a priori exclude cases that do not comply with the due care criteria.2 We believe that it is of the utmost importance that in research, we adopt a shared framework of the definition and concept of sedation to validly compare practices within and between countries. This is the main reason why we proposed a protocol-based definition.1 This would allow us to precisely identify where patients may be at risk of receiving sedation that is not in accordance with due care criteria, why that is the case, and whether this is clinically and ethically problematic. Such data can promote evidence-based policy-making and improvements in end-of-life care.
Second, we agree with Dr. Twycross’s view that sedation should be provided proportionally to each situation. However, proportionality is a complex notion and it is still poorly understood how the concept of proportionality is applied in each country, that is, whether sedation that is regarded as being proportional in one culture can be regarded differently in another culture.3 Multiple empirical studies suggest that the concept of a good death is a significant predictor of a physician’s decision about what is appropriate in end-of-life practices, and the concept of a good death would differ among cultures and among individuals even in the same culture.4,5 For instance, in the Japanese context, dying in one’s sleep is one of the traditional core concepts of a good death.6 Although this does not automatically mean that all types of sedation are ethically and emotionally accepted in Japan, nor that we recommend deep sedation, such cultural traditions may play some role in decision-making regarding sedation in every clinical practice. Cross-cultural studies are thus needed to obtain more insights into what factors determine proportionality throughout the world.
Third, we need to clarify the efficacy and safety of intervention protocols for sedation practice, including the potential effects on symptom experience and patient survival. In addition to the arguments brought forward by Dr. Twycross, we would like to add to the discussion that the proportional use of midazolam involves a theoretical risk of undertreatment, that is, a patient might die before symptom palliation is sufficiently achieved. In our pilot study in a palliative care unit (Imai K, Morita T. in preparation), complete symptom relief at four hours after the start of sedation was achieved in 63% (12/19) of patients who received a proportional use of midazolam protocol vs. 82% (9/11) of patients who received a rapid titration protocol. Deep sedation as a result occurred in 26% of the proportional sedation group vs. 82% of the rapid sedation group. This preliminary result should be replicated in further research, but suggests that the proportional use of sedatives can actually maintain patient consciousness, but that symptom relief might not be sufficient in all patients. This could mean that, when determining the balance between achieving symptom relief and maintaining consciousness, patients’ preferences are an important factor in the decision-making process.
In conclusion, while the UNBIASED study was one of the first comparative studies in this field,7,8 its qualitative nature limits the drawing of generalized conclusions from the data. Currently, a study team from Japan and The Netherlands is preparing an international cross-cultural study, including countries beyond Europe, to shed light on sedation practices and opinions in multiple countries. We hope that this will provide an empirical basis for discussions about how sedation can contribute to patients’ good death.

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Journal Journal of Pain and Symptom Management

Original article: "Continuous Deep Sedation: A Proposal for Performing More Rigorous Empirical Research" by Tatsuya Morita, et al. DOI: 10.1016/j.jpainsymman.2016.08.012

Morita, T, Rietjens, J.A.C, Imai, K, Mori, M, & Tsuneto, S. (2017). Authors' Reply to Twycross. Journal of Pain and Symptom Management, 53(6), e15–e16. doi:10.1016/j.jpainsymman.2017.02.007