"Is this sedation?" : A Group Delphi process to define cut-off doses and dosing intervals for potentially sedating drugs in palliative care

Background: In palliative care, it can be challenging to distinguish between reduced consciousness related to the illness and sedation due to a potentially sedating drug (intended, or unintended). These differentiations are important because unintended sedation requires consideration of alternative treatment options, and intentional sedation demands compliance with guidelines. The aim of the study, which was part of the consortium project iSedPall, was to determine cut-off values for drugs’ doses/dosing intervals which are expected to result in defined depth of sedation/continuous effect. Methods: Group Delphi conducted in Germany with prior online survey. Based on a review of the literature, statements regarding cut-off values for drugs´ doses/dosing intervals which are expected to result in a defined depth of sedation/continuous effect were developed for 11 drugs. Consensus was defined as ≥ 75% agreement. Statements with lower agreement entered the next round of discussion. Between the rounds (5 small groups, 3 – 4 participants each), the results were presented and discussed. If necessary, statements were adapted for the following round. Participating experts were physicians, pharmacists, and nurses experienced in palliative care, mostly with over 10 years of professional experience. Results: 25/30 invited experts participated in the online survey, 17 in the Group Delphi. 12/33 statements were consented in the survey. The initial questionnaire for the Group Delphi comprised 22 statements on ten drugs. After three rounds, consensus was reached for all statements, determining cut-off doses/dosing intervals for lorazepam, midazolam, diazepam, levomepromazine, haloperidol, melperone, pipamperone, propofol, dexmedetomidine, and trazodone. Conclusions: This study for the first time provides evidence- and expert consensus-based data to support clinical judgements regarding sedating effects of a range of potentially sedating drugs commonly used in palliative care.