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Background and Objective: The indication "existential suffering (ES)" for palliative sedation therapy is included in most frameworks for palliative sedation and has been controversially discussed for decades. The appellative character of ES demands rapid relief and sedation often appears to be the best or only solution. ES is still poorly understood and so often neglected by health care professionals due to a lack of consensus regarding assessment, definition and treatment in the international medical literature. Based on a selective review of the literature on ES we propose a different view on the underlying processes of ES and the resulting consequences on medical treatment., Methods: A narrative review was performed after PubMed search using key terms related to ES and sedation, covering the period from 1950 to April 2023, additionally a selective search in specialist literature on Existential Analysis. Reverse and forward snowballing followed. The language of analyzed publications was restricted to English and German., Key Content and Findings: ES is a multidimensional experience that tends to turn into despair and ultimately into a wish to die due to perceived hopelessness and meaninglessness. Pharmacological treatment or sedation do not meet the holistic needs of existential sufferers. The risk of harmful effects by continuous deep sedation seems to be significantly increased for existentially suffering patients. Professional caregivers are burdened by the appellative character of ES, limited treatment options and perceived empathic distress. Without a holistic understanding of the human condition in palliative care, ES cannot be fundamentally alleviated, and existential sufferers have no opportunity to transform and thus mitigate their condition. The recognition of underlying causes of suffering-moods is facilitated by the comprehensive approach of Existential Analysis., Conclusions: The presented concept of Existential Analysis and the triad of ES are useful instruments for health care professionals to recognize and support underlying moods of existentially suffering patients. Further studies are required. Comprehensive training for professional caregivers on ES is essential to enable them to reflect on their own existential concerns and finiteness as well as those of patients. Continuous deep sedation for ES must remain the exception, equivalent to a last resort option.

Background and Objective: The Working Group on Ethics in Anesthesia and Intensive Care Medicine of the Austrian Society for Anesthesiology Resuscitation and Intensive Care Medicine (ÖGARI) already developed documentation tools for the adaption of therapeutic goals 10 years ago. Since then the practical implementation of Comfort Terminal Care in the daily routine in particular has raised numerous questions, which are discussed in this follow-up paper and answered in an evidence-based manner whenever possible., Results: The practical implementation of pain therapy and reduction of anxiety, stress and respiratory distress that are indicated in the context of Comfort Terminal Care are described in more detail. The measures that are not (or no longer) indicated, such as oxygen administration and ventilation as well as the administration of fluids and nutrition, are also commented on. Furthermore, recommendations are given regarding monitoring, (laboratory) findings and drug treatment and the importance of nursing actions in the context of Comfort Terminal Care is mentioned. Finally, the support for the next of kin and the procedure in the time after death are presented., Discussion: A change in treatment goals with a timely switch to Comfort Terminal Care enables good and humane care for seriously ill patients and their relatives at the end of life and the appreciation of their previous life with the possibility of positive experiences until the end., (© 2024. The Author(s).)

Genome analysis of Corynebacterium lactis revealed a bacteriocin gene cluster encoding a putative bacteriocin of the linaridin family of ribosomally synthesized and posttranslationally modified peptides (RiPPs). The locus harbors typical linaridin modification enzymes but lacks genes for a decarboxylase and methyltransferase, which is unusual for type B linaridins. Supernatants of Corynebacterium lactis RW3-42 showed antimicrobial activity against Corynebacterium glutamicum. Deletion of the precursor gene crdA clearly linked the antimicrobial activity of the producer strain to the identified gene cluster. Following purification, we observed potent activity of the peptide against Actinobacteria , mainly other members of the genus Corynebacterium , including the pathogenic species Corynebacterium striatum and Corynebacterium amycolatum. Also, low activity against some Firmicutes was observed, but there was no activity against Gram-negative species. The peptide is resilient towards heat but sensitive to proteolytic degradation by trypsin and proteinase K. Analysis by mass spectrometry indicates that corynaridin is processed by cleaving off the leader sequence at a conserved motif and posttranslationally modified by dehydration of all threonine and serin residues, resulting in a monoisotopic mass of 3,961.19 Da. Notably, time-kill kinetics and experiments using live biosensors to monitor membrane integrity suggest bactericidal activity that does not involve formation of pores in the cytoplasmic membrane. As Corynebacterium species are ubiquitous in nature and include important commensals and pathogens of mammalian organisms, secretion of bacteriocins by species of this genus could be a hitherto neglected trait with high relevance for intra- and interspecies competition and infection. IMPORTANCE Bacteriocins are antimicrobial peptides produced by bacteria to fend off competitors in ecological niches and are considered to be important factors influencing the composition of microbial communities. However, bacteriocin production by bacteria of the genus Corynebacterium has been a hitherto neglected trait, although its species are ubiquitous in nature and make up large parts of the microbiome of humans and animals. In this study, we describe and characterize a novel linaridin family bacteriocin from Corynebacterium lactis and show its narrow-spectrum activity, mainly against other actinobacteria. Moreover, we were able to extend the limited knowledge on linaridin bioactivity in general and for the first time describe the bactericidal activity of such a bacteriocin. Interestingly, the peptide, which was named corynaridin, appears bactericidal, but without formation of pores in the bacterial membrane.

Cyclic di-adenosine monophosphate (c-di-AMP) is a bacterial second messenger discovered in Bacillus subtilis and involved in potassium homeostasis, cell wall maintenance and/or DNA stress response. As the role of c-di-AMP has been mostly studied in Firmicutes, we sought to increase the understanding of its role in Actinobacteria, namely in Corynebacterium glutamicum . This organism is a well-known industrial production host and a model organism for pathogens, such as C. diphtheriae or Mycobacterium tuberculosis . Here, we identify and analyze the minimal set of two C. glutamicum enzymes, the diadenylate cyclase DisA and the phosphodiesterase PdeA, responsible for c-di-AMP metabolism. DisA synthesizes c-di-AMP from two molecules of ATP, whereas PdeA degrades c-di-AMP, as well as the linear degradation intermediate phosphoadenylyl-(3'→5')-adenosine (pApA) to two molecules of AMP. Here, we show that a ydaO/kimA -type c-di-AMP-dependent riboswitch controls the expression of the strictly regulated cell wall peptidase gene nlpC in C. glutamicum . In contrast to previously described members of the ydaO/kimA -type riboswitches, our results suggest that the C. glutamicum nlpC riboswitch likely affects the translation instead of the transcription of its downstream gene. Although strongly regulated by different mechanisms, we show that the absence of nlpC , the first known regulatory target of c-di-AMP in C. glutamicum , is not detrimental for this organism under the tested conditions.

During the light-dependent reaction of photosynthesis, green plants couple photoinduced cascades of redox reactions with transmembrane proton translocations to generate reducing equivalents and chemical energy in the form of NADPH (nicotinamide adenine dinucleotide phosphate) and ATP (adenosine triphosphate), respectively. We mimic these basic processes by combining molecular ruthenium polypyridine-based photocatalysts and inverted vesicles derived from Escherichia coli. Upon irradiation with visible light, the interplay of photocatalytic nicotinamide reduction and enzymatic membrane-located respiration leads to the simultaneous formation of two biologically active cofactors, NADH (nicotinamide adenine dinucleotide) and ATP, respectively. This inorganic-biologic hybrid system thus emulates the cofactor delivering function of an active chloroplast., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Background: The bacteriocin nisin is naturally produced by Lactococcus lactis as an inactive prepeptide that is modified posttranslationally resulting in five (methyl-)lanthionine rings characteristic for class Ia bacteriocins. Export and proteolytic cleavage of the leader peptide results in release of active nisin. By targeting the universal peptidoglycan precursor lipid II, nisin has a broad target spectrum including important human pathogens such as Listeria monocytogenes and methicillin-resistant Staphylococcus aureus strains. Industrial nisin production is currently performed using natural producer strains resulting in rather low product purity and limiting its application to preservation of dairy food products., Results: We established heterologous nisin production using the biotechnological workhorse organism Corynebacterium glutamicum in a two-step process. We demonstrate successful biosynthesis and export of fully modified prenisin and its activation to mature nisin by a purified, soluble variant of the nisin protease NisP (sNisP) produced in Escherichia coli. Active nisin was detected by a L. lactis sensor strain with strictly nisin-dependent expression of the fluorescent protein mCherry. Following activation by sNisP, supernatants of the recombinant C. glutamicum producer strain cultivated in standard batch fermentations contained at least 1.25 mg/l active nisin., Conclusions: We demonstrate successful implementation of a two-step process for recombinant production of active nisin with C. glutamicum. This extends the spectrum of bioactive compounds that may be produced using C. glutamicum to a bacteriocin harboring complex posttranslational modifications. Our results provide a basis for further studies to optimize product yields, transfer production to sustainable substrates and purification of pharmaceutical grade nisin., (© 2022. The Author(s).)

A series of three Ru(II) polypyridine complexes was investigated for the selective photocatalytic oxidation of NAD(P)H to NAD(P) + in water. A combination of (time-resolved) spectroscopic studies and photocatalysis experiments revealed that ligand design can be used to control the mechanism of the photooxidation: For prototypical Ru(II) complexes a 1 O 2 pathway was found. Rudppz ([(tbbpy) 2 Ru(dppz)]Cl 2 , tbbpy=4,4'-di-tert-butyl-2,2'-bipyridine, dppz=dipyrido[3,2-a:2',3'-c]phenazine), instead, initiated the cofactor oxidation by electron transfer from NAD(P)H enabled by supramolecular binding between substrate and catalyst. Expulsion of the photoproduct NAD(P) + from the supramolecular binding site in Rudppz allowed very efficient turnover. Therefore, Rudppz permits repetitive selective assembly and oxidative conversion of reduced naturally occurring nicotinamides by recognizing the redox state of the cofactor under formation of H 2 O 2 as additional product. This photocatalytic process can fuel discontinuous photobiocatalysis., (© 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Bacteriocins are antimicrobial peptides produced by bacteria to inhibit competitors in their natural environments. Some of these peptides have emerged as commercial food preservatives and, due to the rapid increase in antibiotic resistant bacteria, are also discussed as interesting alternatives to antibiotics for therapeutic purposes. Currently, commercial bacteriocins are produced exclusively with natural producer organisms on complex substrates and are sold as semi-purified preparations or crude fermentates. To allow clinical application, efficacy of production and purity of the product need to be improved. This can be achieved by shifting production to recombinant microorganisms. Here, we identify Corynebacterium glutamicum as a suitable production host for the bacteriocin pediocin PA-1. C. glutamicum CR099 shows resistance to high concentrations of pediocin PA-1 and the bacteriocin was not inactivated when spiked into growing cultures of this bacterium. Recombinant C. glutamicum expressing a synthetic pedACD Cgl operon releases a compound that has potent antimicrobial activity against Listeria monocytogenes and Listeria innocua and matches size and mass:charge ratio of commercial pediocin PA-1. Fermentations in shake flasks and bioreactors suggest that low levels of dissolved oxygen are favorable for production of pediocin. Under these conditions, however, reduced activity of the TCA cycle resulted in decreased availability of the important pediocin precursor l-asparagine suggesting options for further improvement. Overall, we demonstrate that C. glutamicum is a suitable host for recombinant production of bacteriocins of the pediocin family., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Post-translationally modified, (methyl-)lanthionine-containing peptides are produced by several Gram-positive bacteria. These so-called lantibiotics have potent activity against various bacterial pathogens including multidrug-resistant strains and are thus discussed as alternatives to antibiotics. Several naturally occurring mechanisms of resistance against lantibiotics have been described for bacteria, including cell envelope modifications, ABC-transporters, lipoproteins and peptidases. Corynebacterium species are widespread in nature and comprise important pathogens, commensals as well as environmentally and biotechnologically relevant species. Yet, little is known about lantibiotic biosynthesis and resistance in this genus. Here, we present a comprehensive in silico prediction of lantibiotic resistance traits in this important group of Gram-positive bacteria. Our analyses suggest that enzymes for cell envelope modification, peptidases as well as ABC-transporters involved in peptide resistance are widely distributed in the genus. Based on our predictions, we analyzed the susceptibility of six Corynebacterium species to nisin and found that those without dedicated resistance traits are more susceptible and unable to adapt to higher concentrations. In addition, we were able to identify lantibiotic resistance operons encoding for peptidases, ABC-transporters and two-component systems with an unusual predicted structure that are conserved in the genus Corynebacterium . Heterologous expression shows that these operons indeed confer resistance to the lantibiotic nisin.

In vitro synthesis of ATP catalyzed by the ATP-synthase requires membrane vesicles, in which the ATP-synthase is present within the bilayer membrane. Inverted vesicle prepared from Gram negative cells (e.g., Escherichia coli or Pseudomonas putida) can be readily obtained and used for in vitro ATP-synthesis. Up to now, quantification of ATP synthesized by membrane vesicles has been mostly analyzed via bioluminescence-based assays. Alternatively, vesicle respiration and the associated ATP level can be determined using biosensors, which not only provide high selectivity, but allow ATP measurements without the sample being illuminated. Here, we present a microbiosensor for ATP in combination with scanning electrochemical microscopy (SECM) using an innovative two-compartment electrochemical cell for the determination of ATP levels at E.coli or P. putida inverted vesicles. For a protein concentration of 22 mg/ml, a total amount of 0.29 ± 0.03 μM/μl ATP per vesicle was determined in case of E.coli; in turn, P. putida derived vesicles yielded 0.48 ± 0.02 μM/μl ATP per vesicle at a total protein concentration of 25.2 mg/ml. Inhibition experiments with Venturicidin A clearly revealed that the respiratory chain enzyme complex responsible for ATP generation is effectively involved., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In palliative medicine planning in advance is important for critical care situations. It is highly significant to make useful and by the patient and his relatives desired decisions. These concern transport in a situation of crisis and the venue of death (either death at home or transfer to a hospital).In this study the effect of a new Emergency Information Form about the place of death was examined. The used Emergency Information Form enabled the patient to express a wish on transfer in the case of crisis in advance and communicate this wish to the Emergency system.A total of 858 patients, taken care of by the mobile palliative-team Hartberg/Weiz/Vorau in the period from 2010 to 2015, were included in the study. The Intervention group-the patients for whom an Emergency Information Form was established-counted 38 patients. Data analysis was retrospective, pseudo anonymized and external.The 4 most important results were:1) The Emergency Information Form increased the probability for the intervention group to die at home (intervention group: 72.2%, controll group 1: 53.0%, controll group 2: 56.6%).2) Important in this change was, that the opinion of the patients was considered. The decision made in the Emergency Information Form correlated with a high significance (p = 0.01) with the actual place of death.3) Furthermore, it came clear that the Emergency Information Form was a useful tool to handle the utilization of special facilities. Within the intervention group young patients (with a lot of symptoms) died in a special facility more often than old patients. These, rather geriatric people, were mostly brought to a general hospital.4) There was no significant relation between the duration of care and the probability that an Emergency Information Form was established (p = 0.63). However, there was a high significance between the number of home visits and the probability that an Emergency Information Form was written (p = 0.02).Due to the fact that there was a small intervention group restricted to only one palliative team further studies could help to make clear advises for palliative teams regarding scope, duration and frequency of home-visits. Thus the term "care continuity" could be concretized in the guidelines.The study brought forward that numerous (and short) contacts with the patient were more convenient than less but long home-visits in order to fulfil the patients wish concerning his place of death.

Background: Emergency departments (ED) serve as a contact point for critically ill patients. According to experience, a fraction of patients visiting ED present with palliative symptoms and require palliative care; however, the prevalence of these patients has not been determined in Austria so far., Methods: In the ED of a tertiary care medical centre in Carinthia all adult patients presenting between 8 January 2018 and 17 January 2018 were classified on arrival with the Manchester triage system (MTS) and were afterwards assessed with a validated 2‑tier screening tool for palliative care. Patient records were screened in April 2018 to find out whether they received palliative care., Results: In total 1277 patients visited the ED during the investigation period. Of these patients 1096 were screened and 145 of these patients (13.2%) showed palliative symptoms and needed a goal-oriented therapy. Of these 145 patients 10.9% were assessed by MTS as emergency, 2.7% as very urgent, 34.7% as urgent, 51% as normal, and 0.7% as not urgent. Only 8 (5.5%) of the patients with palliative medical symptoms actually received palliative care consultation., Conclusions: More than 1 in 10 patients attending an ED suffered from palliative symptoms. Hence it is to be expected that healthcare providers in an ED in Austria will frequently encounter patients with palliative symptoms in emergency admissions. Therefore, it is necessary to develop suitable structures to provide these patients with the best possible care.

Bacteriocins are antimicrobial peptides naturally produced by many bacteria and were shown to be effective against various pathogens including Listeria monocytogenes . L. monocytogenes is a food-borne pathogen that frequently causes disease outbreaks around the world with fatal outcomes in at-risk individuals. Thus, bacteriocins are a promising solution to prevent contaminations with L. monocytogenes and other microorganisms during food production and preservation. In the present study, we constructed L. monocytogenes EGD-e/pNZ-P help -pHluorin, a strain that constitutively expresses the pH-sensitive fluorescent protein pHluorin, as a sensor strain to detect disruption of the pH gradient by the membrane-damaging activity of bacteriocins. The ratiometric fluorescence properties of pHluorin were validated both in crude extracts and permeabilized cells of this sensor strain. L. monocytogenes EGD-e/pNZ-P help -pHluorin was used to assess membrane damaging activity of the bacteriocins nisin A and pediocin PA-1 and to determine the minimal concentrations required for full disruption of the pH gradient across the membrane. Moreover, the sensor strain proved useful to analyze the presence of compounds affecting membrane integrity in supernatants of a nisin Z-producing Lactococcus lactis strain at different timepoints during growth. Supernatants of this strain that were active in disrupting the pH gradient across the membrane were also shown to inhibit growth of L. monocytogenes . In summary, the presented results suggest that the generated sensor strain is a convenient, fast and reliable tool to identify and characterize novel bacteriocins and other compounds that target membrane integrity.

In some cases terminally ill patients fear of prolonged dying and suffering can manifest itself in the voluntary refusal of food and fluids, aiming to accelerate the dying process. This represents a considerable area of conflict, because of the ethical responsibility to not aid a person's death but also to respect a patients autonomy.There is a clear separation between an assisted suicide and following a patient's wishes. Not to accept the voluntary refusal of FVNF would have to be considered as forced treatment of patients while they are capable of self-determination.Several symptoms associated with or caused by voluntary refusal of food and fluids do require palliative care. It is important to be aware, that caring for dying patients refusing food and fluids and accepting their choice is not synonymous with assisted suicide. Rather is it part of medical and nursing care for patients during their dying-process.An interprofessional working group of the Austrian Palliative Society (OPG) intends to shed light on the legal, ethical, medical and nursing related aspects concerning this subject of growing public and professional interest.

Background: Palliative sedation therapy (PST) is an important and ethically accepted therapy in the care of selected palliative care patients with otherwise unbearable suffering from refractory distress. PST is increasingly used in end-of-life care. Austria does not have a standardized ethical guideline for this exceptional practice near end of life, but there is evidence that practice varies throughout the country., Objective: The Austrian Palliative Society (OPG) nominated a multidisciplinary working group of 16 palliative care experts and ethicists who established the national guideline on the basis of recent review work with the aim to adhere to the Europeans Association of Palliative Care's (EAPC) framework on palliative sedation therapy respecting Austrians legal, structural and cultural background., Methods: Consensus was achieved by a four-step sequential Delphi process. The Delphi-process was strictly orientated to the recently published EUROIMPACT-sedation-study-checklist and to the AGREE-2-tool. Additionally national stakeholders participated in the reflection of the results., Results: As a result of a rigorous consensus process the long version of the Austrian National Palliative Sedation Guideline contains 112 statements within eleven domains and is supplemented by a philosophers excursus on suffering., Conclusions: By establishing a national guideline for palliative sedation therapy using the Delphi technique for consensus and stakeholder involvement the Austrian Palliative Society aims to ensure nationwide good practice of palliative sedation therapy. Screening for the practicability and efficacy of this guideline will be a future task.

Background: Sedation is used to an increasing extent in end-of-life care. Definitions and indications in this field are based on expert opinions and case series. Little is known about this practice at palliative care units in Austria., Methods: Patients who died in Austrian palliative care units between June 2012 and June 2013 were identified. A predefined set of baseline characteristics and information on sedation during the last two weeks before death were obtained by reviewing the patients' charts., Results: The data of 2414 patients from 23 palliative care units were available for analysis. Five hundred two (21 %) patients received sedation in the last two weeks preceding their death, 356 (71 %) received continuous sedation until death, and 119 (24 %) received intermittent sedation. The median duration of sedation was 48 h (IQR 10-72 h); 168 patients (34 %) were sedated for less than 24 h. Indications for sedation were delirium (51 %), existential distress (32 %), dyspnea (30 %), and pain (20 %). Midazolam was the most frequently used drug (79 %), followed by lorazepam (13 %), and haloperidol (10 %). Sedated patients were significantly younger (median age 67 years vs. 74 years, p ≤ 0.001, r = 0.22), suffered more often from an oncological disease (92 % vs. 82 %, p ≤ 0.001, φ = 0.107), and were hospitalized more frequently (94 % vs. 76 %, p ≤ 0.001, φ = 0.175). The median number of days between admission to a palliative care ward/mobile palliative care team and death did not differ significantly in sedated versus non-sedated patients (10 vs. 9 days; p = 0.491)., Conclusion: This study provides insights into the practice of end-of-life sedation in Austria. Critical appraisal of these data will serve as a starting point for the development of nation-wide guidelines for palliative sedation in Austria.

Purpose: This study aims to determine the numbers of patients with advanced cancer receiving polypharmacy at the end of their lives and analyze differences in drug prescription at a general oncology ward and a dedicated palliative care ward., Methods: A retrospective single-center cohort study at a university hospital with a large cancer center was conducted. The charts of 100 patients who had died because of advanced cancer were reviewed; data concerning sociodemographic variables and medications were collected at four predefined time points (9, 6, 3, 0 days before death)., Results: Nine days before death, polypharmacy was registered in 95 % of patients; they had prescriptions for 11 (9-13) different medications per day (median, IQR). Although this number dropped significantly, on the last day as many as 61 % of the patients were still taking more than 4 drugs (median 6.5, IQR 4-9). No significant difference was noted between the oncology ward and the palliative care ward. Polypharmacy was largely dependent on the patients' ECOG performance status as well as the type of ward, the number of days before death, and age. It was not influenced by gender, the duration of hospital stays, and the devices facilitating drug administration. The medications fulfilled the requirements of palliative care in the majority of patients; 90 % received treatment for pain and anxiety. Patients treated at the palliative ward received more opioids and psychoactive drugs while those at the oncology ward received more anti-cancer drugs and fluids., Conclusions: Polypharmacy still is a problem in the large majority of patients with terminal cancer. Further studies should be focused on the patients' quality of life, drug interactions, and adverse events.

Adequate symptom relief is a central aspect of medical care of all patients especially in those with an incurable disease. However, as an illness progresses and the end of life approaches, physical or psychoexistential symptoms may remain uncontrollable requiring palliative sedation. Although palliative sedation has become an increasingly implemented practice in the care of terminally ill patients, sedation in the management of refractory psychological symptoms and existential distress is still a controversial issue and much debated. This case report presents a patient who received palliative sedation for the treatment of existential distress and discusses considerations that may arise from such a therapeutic approach.

Personalized cancer treatment utilizing targeted therapies in a tailored approach is based on tumor and/or patient-specific molecular profiles. Recent clinical trials continue to look for new potential targets in heavily pretreated patients or rare disease entities. Careful selection of patients who may derive benefit from such therapies constitutes a challenge. This case report presents an experimental personalized cancer treatment in an advanced cancer patient and provides a list of issues for discussion: How can we combine treatment goals and simultaneously meet the individual needs in advanced cancer reconciling both perspectives: oncology and palliative care?

The occurrence of cachexia at the end of life of patients suffering from cancer is a common seen problem. Within the last years new definitions, diagnostic criteria and classification systems of cachexia have been developed to improve the clinical practice. Still therapeutic interventions are limited; the role of parenteral nutrition (PN) remains controversial. PN cannot be generally recommended in patients with incurable malignancies, not even in ill-nourished patients with inadequate oral or enteral nutrition due to a changed metabolism. Treating a cachectic endstage patient suffering from head-neck-cancer we were faced with different problems.

Sedation in palliative care is generally considered as an important therapy in terminally ill patients with refractory symptoms. However the sedation of patients with intractable psycho-existential suffering is still under discussion. This paper discusses the case of a 56-year-old patient in the final phase of carcinoma of the ovaries, who required palliative sedation for refractory, mainly psycho-existential suffering. It describes the course on our ward and the difficult process of decision-making. We discuss our approach based on literature.

In this case study we report on a patient with advanced myxofibrosarcoma and lung metastases, suffering from severe dyspnoea. Symptoms were not manageable by means of standard palliative care, which made palliative sedation therapy necessary in order to alleviate dyspnoea. On the basis of this case study, indications, drugs, therapy monitoring and ethical aspects of palliative sedation therapy are discussed.

We describe a family with a severely disabled child who demonstrates many of the characteristics of resilient families: strong relationships, good communication, and profound love of the disabled child. But this family has a characteristic that is infrequently described in the literature yet common in practice: the mother initiated many medical decisions based on knowledge gathered on the Internet. Parental education on the Internet can now allow families to gain a sense of mastery over their child's disease.

Severe pain caused by multiple metastases in bones in a pediatric patient suffering from rhabdomyosarcoma, a solid tumor of childhood, made palliative sedation therapy after developing metastases in lung necessary. The premises for this therapy, the difference in the choice of drugs compared to adults and psychology of the dying child are discussed.

Ketamine is a hypnotic pharmacon with high analgesic potency. Ketamine is an agent blocking NMDA-receptors and involves opioid receptors, the voltage-gated sodium-channel, cholinergic receptors and the monoaminergic descending inhibitory pathways. Besides its influence in chronification of pain, NMDA-R is crucial in induction and maintainance of visceral pain, attentional perceptual processes and emotional valuation of pain. The analgesic potency of S-+-Ketamine doubles racemic Ketamine's analgesic potency. Thus the incidence of CNS-side effects ought to be reduced to 50% in equianalgesic dosages. Evidence supports the assumption that continuous infusion of S-+-Ketamine 2.5-5 mg/hour is effective in treating visceral pain of high intensity. In the presence of chronic pain states the effect ought to be more marked. There is evidence that the probability of psychotomimetic side effects does not exceed 10%. The rate of side effects can further be minimized through careful titration and prophylaxis (or treatment) with Diazepam 1 mg i.v.

On the basis of a case study, the complex problems of the final stages of a COPD will be demonstrated and discussed. Dyspnea and anxiousness are the primary symptoms. If they can be adequately brought under control by opiates and benzodiazepines, a palliative sedation is then not necessary. The communicative and ethical demands on the team responsible are high. It is important to be aware of the specific needs of the patient and of his/her family members, and to competently accompany the patient throughout the decision-making process--such as the decision to end respiratory therapy, for example. Clarifying the situation with the patient and finding out his/her wishes, accompanied by the corresponding documentation, is advisable.