The apoptosis-inducing activity towards leukemia and lymphoma cells in a cyanobacterial culture collection is not associated with mouse bioassay toxicity

Cyanobacteria (83 strains and seven natural populations) were screened for content of apoptosis (cell death)-inducing activity towards neoplastic cells of the immune (jurkat acute T-cell lymphoma) and hematopoetic (acute myelogenic leukemia) lineage. Apoptogenic activity was frequent, even in strains cultured for decades, and was unrelated to whether the cyanobacteria had been collected from polar, temperate, or tropic environments. The activity was more abundant in the genera Anabaena and Microcystis compared to Nostoc, Phormidium, Planktothrix, and Pseudanabaena. Whereas the T-cell lymphoma apoptogens were frequent in organic extracts, the cell death-inducing activity towards leukemia cells resided mainly in aqueous extracts. The cyanobacteria were from a culture collection established for public health purposes to detect toxic cyanobacterial blooms, and 54 of them were tested for toxicity by the mouse bioassay. We found no correlation between the apoptogenic activity in the cyanobacterial isolates with their content of microcystin, nor with their ability to elicit a positive standard mouse bioassay. Several strains produced more than one apoptogen, differing in biophysical or biological activity. In fact, two strains contained microcystin in addition to one apoptogen specific for the AML cells, and one apoptogen specific for the T-cell lymphoma. This study shows the potential of cyanobacterial culture collections as libraries for bioactive compounds, since strains kept in cultures for decades produced apoptogens unrelated to the mouse bioassay detectable bloom-associated toxins

Clinical and ethical aspects of palliative sedation with propofol—A retrospective quantitative and qualitative study

Background The anesthetic propofol is often mentioned as a drug that can be used in palliative sedation. The existing literature of how to use propofol in palliative sedation is scarce, with lack of information about how propofol could be initiated for palliative sedation, doses and treatment outcomes. Aim To describe the patient population, previous and concomitant medication, and clinical outcome when propofol was used for palliative sedation. Methods A retrospective study with quantitative and qualitative data. All patients who during a 4.5‐year period received propofol for palliative sedation at the Department of palliative medicine, Akershus University Hospital, Norway were included. Results Fourteen patients were included. In six patients the main indication for palliative sedation was pain, in seven dyspnoea and in one delirium. In eight of these cases propofol was chosen because of the pharmacokinetic properties (rapid effect), and in the remaining cases propofol was chosen because midazolam in spite of dose titration failed to provide sufficient symptom relief. In all patients sedation and adequate symptom control was achieved during manual dose titration. During the maintenance phase three of 14 patients had spontaneous awakenings. At death, propofol doses ranged from 60 to 340 mg/hour. Conclusions Severe suffering at the end of life can be successfully treated with propofol for palliative sedation. This can be performed in palliative medicine wards, but skilled observation and dose titration throughout the period of palliative sedation is necessary. Successful initial sedation does not guarantee uninterrupted sedation until death

Clinical and ethical aspects of palliative sedation with propofol—A retrospective quantitative and qualitative study

Background The anesthetic propofol is often mentioned as a drug that can be used in palliative sedation. The existing literature of how to use propofol in palliative sedation is scarce, with lack of information about how propofol could be initiated for palliative sedation, doses and treatment outcomes. Aim To describe the patient population, previous and concomitant medication, and clinical outcome when propofol was used for palliative sedation. Methods A retrospective study with quantitative and qualitative data. All patients who during a 4.5‐year period received propofol for palliative sedation at the Department of palliative medicine, Akershus University Hospital, Norway were included. Results Fourteen patients were included. In six patients the main indication for palliative sedation was pain, in seven dyspnoea and in one delirium. In eight of these cases propofol was chosen because of the pharmacokinetic properties (rapid effect), and in the remaining cases propofol was chosen because midazolam in spite of dose titration failed to provide sufficient symptom relief. In all patients sedation and adequate symptom control was achieved during manual dose titration. During the maintenance phase three of 14 patients had spontaneous awakenings. At death, propofol doses ranged from 60 to 340 mg/hour. Conclusions Severe suffering at the end of life can be successfully treated with propofol for palliative sedation. This can be performed in palliative medicine wards, but skilled observation and dose titration throughout the period of palliative sedation is necessary. Successful initial sedation does not guarantee uninterrupted sedation until death

Ought the level of sedation to be reduced during deep palliative sedation? A clinical and ethical analysis

Background Deep palliative sedation (DPS) is applied as a response to refractory suffering at the end of life when symptoms cannot be relieved in an awake state. DPS entails a dilemma of whether to provide uninterrupted sedation—in which case DPS would turn into deep and continuous palliative sedation (DCPS) —to minimise the risk that any further intolerable suffering will occur or whether to pause sedation to avoid unnecessary sedation. DPS is problematic in that it leaves the patient ‘socially dead’ by eradicating their autonomy and conscious experiences. Aim To perform a normative ethical analysis of whether guidelines should recommend attempting to elevate consciousness during DPS. Design A structured analysis based on the four principles of healthcare ethics and consideration of stakeholders’ interests. Results When DPS is initiated it reflects that symptom relief is valued above the patient’s ability to exercise autonomy and experience social interaction. However, if a decrease in symptom burden occurs, waking could be performed without patients experiencing suffering. Such pausing of deep sedation would satisfy the principles of autonomy and beneficence. Certain patients require substantial dose increases to maintain sedation. Waking such patients risks causing distressing symptoms. This does not happen if deep sedation is kept uninterrupted. Thus, the principle of non-maleficence points towards not pausing sedation. The authors’ clinical ethics analysis demonstrates why other stakeholders’ interests do not appear to override arguments in favour of providing uninterrupted sedation. Conclusion Stopping or pausing DPS should always be considered, but should not be routinely attempted