Pharmacokinetic considerations and recommendations in palliative care, with focus on morphine, midazolam and haloperidol

Introduction: A variety of medications are used for symptom control in palliative care, such as morphine, midazolam and haloperidol. The pharmacokinetics of these drugs may be altered in these patients as a result of physiological changes that occur at the end stage of life. Areas covered: This review gives an overview of how the pharmacokinetics in terminally ill patients may differ from the average population and discusses the effect of terminal illness on each of the four pharmacokinetic processes absorption, distribution, metabolism, and elimination. Specific considerations are also given for three commonly prescribed drugs in palliative care: morphine, midazolam and haloperidol). Expert opinion: The pharmacokinetics of drugs in terminally ill patients can be complex and limited evidence exists on guided drug use in this population. To improve the quality of life of these patients, more knowledge and more pharmacokinetic/pharmacodynamics studies in terminally ill patients are needed to develop individualised dosin

Scopolaminebutyl given prophylactically for death rattle: Study protocol of a randomized double-blind placebo-controlled trial in a frail patient population (the SILENCE study)

Background: Death rattle (DR), caused by mucus in the respiratory tract, occurs in about half of patients who are in the dying phase. Relatives often experience DR as distressing. Anticholinergics are recommended to treat DR, although there is no evidence for the effect of these drugs. Anticholinergic drugs decrease the production of mucus but do not affect existing mucus. We therefore hypothesize that these drugs are more effective when given prophylactically. Methods: We set up a randomized double-blind, placebo-controlled, multi-center study evaluating the efficacy of prophylactically given subcutaneous scopolaminebutyl for the prevention of DR in the dying phase. The primary outcome is the occurrence of DR defined as grade ≥ 2 according to the scale of Back measured by a nurse at 2 consecutive time points with an interval of 4 h. Secondary outcomes include adverse effects, quality of dying, quality of life in the last three days and bereavement. A sub-study will explore the experience of participating in a clinical trial in the dying phase from the perspective of relatives. Four hospices will include 200 patients. Discussion: This is the first double-blind placebo-controlled study to prevent DR in patients in the hospice setting. Research in dying patients is challenging. We will apply ethical and organizational strategies as suggested in the literature

Understanding relatives' experience of death rattle

BACKGROUND: Death rattle is a frequently occurring symptom in the last phase of life. The experience of death rattle of relatives has been found to vary. It is unclear if treatment with medication is useful. The most fitting solution for this symptom is still under debate. AIM: This study aims to better understand the experience of relatives of their loved ones' death rattle. DESIGN: A qualitative interview study with a phenomenological approach was performed. Data were collected through semi-structured interviews which were audio recorded, transcribed and analyzed using qualitative content analysis. PARTICIPANTS: Nineteen family members of 15 patients were interviewed. RESULTS: Most relatives had experienced death rattle as a distressing symptom. Concerns about how long the rattling would last resulted in more distress. Experience of death rattle was less fierce when other symptoms such as pain or dyspnea prevailed. Hearing the sound of death rattle sometimes reminded relatives of previously witnessed dying trajectories, which seemed to increase their current level of distress. The experience of death rattle is not always influenced by the amount and quality of information given about the symptom. CONCLUSION: Death rattle is a stressful symptom and the experience of relatives is influenced by more factors than the sound itself. Communication and information alone seem inefficient to address relatives' distress. The best approach for dealing with this symptom is unclear. Further research needs to show if prophylactically given drugs may be helpful in its prevention