End-of-life practices in 11 German intensive care units : Results from the ETHICUS-2 study.

BACKGROUND: End-of-life care is common in German intensive care units (ICUs) but little is known about daily practice. OBJECTIVES: To study the practice of end-of-life care. METHODS: Prospectively planned, secondary analysis comprising the German subset of the worldwide Ethicus­2 Study (2015-2016) including consecutive ICU patients with limitation of life-sustaining therapy or who died. RESULTS: Among 1092 (13.7%) of 7966 patients from 11 multidisciplinary ICUs, 967 (88.6%) had treatment limitations, 92 (8.4%) died with failed CPR, and 33 (3%) with brain death. Among patients with treatment limitations, 22.3% (216/967) patients were discharged alive from the ICU. More patients had treatments withdrawn than withheld (556 [57.5%] vs. 411 [42.5%], p < 0.001). Patients with treatment limitations were older (median 73 years [interquartile range (IQR) 61-80] vs. 68 years [IQR 54-77]) and more had mental decision-making capacity (12.9 vs. 0.8%), advance directives (28.6 vs. 11.2%), and information about treatment wishes (82.7 vs 33.3%, all p < 0.001). Physicians reported discussing treatment limitations with patients with mental decision-making capacity and families (91.3 and 82.6%, respectively). Patient wishes were unknown in 41.3% of patients. The major reason for decision-making was unresponsiveness to maximal therapy (34.6%). CONCLUSIONS: Treatment limitations are common, based on information about patients' wishes and discussion between stakeholders, patients and families. However, our findings suggest that treatment preferences of nearly half the patients remain unknown which affects guidance for treatment decisions.

[New antibiotics for severe infections due to multidrug-resistant pathogens : Definitive treatment and escalation]. / Neue Antibiotika bei schweren Infektionen durch multiresistente Erreger : Definitive Therapie und Eskalation.

Multidrug-resistant pathogens often lead to treatment failure of antimicrobial regimens. After a period of imbalance between the occurrence/spread of resistance mechanisms and the development of new substances, some new substances have meanwhile been approved and many more are currently undergoing clinical testing. They are particularly effective against specific resistance mechanisms/pathogens and should be preserved for definitive treatment of an isolated pathogen. In the absence of alternatives reserve antibiotics, such as aztreonam and colistin have experienced a renaissance. They are again used in special infection scenarios and clinically tested in combination with new substances. Despite the introduction and development of new substances the building of resistance will at some time also render these (at least partially) ineffective. Therefore, their implementation must be carried out according to the antibiotic or infectious diseases stewardship.

[Infections due to multidrug-resistant pathogens : Pathogens, resistance mechanisms and established treatment options]. / Infektionen durch multiresistente Erreger : Erreger, Resistenzmechanismen und etablierte Therapieoptionen.

The increase in resistant pathogens has long been a global problem. Complicated life-threatening infections due to multidrug-resistant pathogens (MRD) meanwhile occur regularly in intensive care medicine. An important and also potentially modifiable factor of the rapid spread of resistance is the irrational use of broad spectrum antibiotics in human medicine. In addition to many other resistance mechanisms, beta-lactamases play an important role in Gram-negative pathogens. They are not uncommonly the leading reason of difficult to treat infections and the failure of known routinely used broad spectrum antibiotics, such as cephalosporins, (acylamino)penicillins and carbapenems. Strategies for containment of MRDs primaríly target the rational use of antibiotics. In this respect interdisciplinary treatment teams, e.g. antibiotic stewardship (ABS) and infectious diseases stewardship (IDS) play a major role.

[Principles and pitfalls of arterial blood pressure measurement]. / Grundlagen und Fallstricke der arteriellen Blutdruckmessung.

The determination of arterial blood pressure is a fundamental part of basic cardiovascular monitoring in perioperative, intensive care and emergency medicine. Blood pressure can be measured directly via an arterial catheter, which is the most accurate method. Blood pressure is most commonly monitored using noninvasive intermittent methods with an occluding upper arm cuff. Noninvasive intermittent blood pressure measurements can also be performed either manually using palpation and auscultation or automatically based on an oscillometric algorithm. Furthermore, methods such as the vascular unloading technique with a finger plethysmographic sensor are available for continuous and noninvasive blood pressure monitoring. This article explains the principles of the individual methods, the sources of errors, advantages and disadvantages and discusses the fields of application in the clinical routine.

[Surviving Sepsis Campaign update 2018: the 1 h bundle : Background to the new recommendations]. / Surviving Sepsis Campaign Update 2018: das 1­h-Bundle : Hintergrund zu den neuen Empfehlungen.

A new update of the sepsis bundle was published by the Surviving Sepsis Campaign (SSC) in April 2018. The original 3 h and 6 h bundles have been restructured and combined into a 1­h bundle. The recommendations comprehensively focus on diagnostic and therapeutic measures which should be carried out within 1 h after recognition of sepsis. This article presents the background and discusses criticisms of the new recommendations.

Bacterial sepsis : Diagnostics and calculated antibiotic therapy.

The mortality of patients with sepsis and septic shock is still unacceptably high. An effective calculated antibiotic treatment within 1 h of recognition of sepsis is an important target of sepsis treatment. Delays lead to an increase in mortality; therefore, structured treatment concepts form a rational foundation, taking relevant diagnostic and treatment steps into consideration. In addition to the assumed infection and individual risks of each patient, local resistance patterns and specific problem pathogens must be taken into account during the selection of anti-infective treatment. Many pathophysiologic alterations influence the pharmacokinetics (PK) of antibiotics during sepsis. The principle of standard dosing should be abandoned and replaced by an individual treatment approach with stronger weighting of the pharmacokinetics/pharmacodynamics (PK/PD) index of the substance groups. Although this is not yet the clinical standard, prolonged (or continuous) infusion of ß­lactam antibiotics and therapeutic drug monitoring (TDM) can help to achieve defined PK targets. Prolonged infusion is sufficient without TDM, but for continuous infusion, TDM is generally necessary. A further argument for individual PK/PD-oriented antibiotic approaches is the increasing number of infections due to multidrug-resistant (MDR) pathogens in the intensive care unit. For effective treatment, antibiotic stewardship teams (ABS teams) are becoming more established. Interdisciplinary cooperation of the ABS team with infectious disease (ID) specialists, microbiologists, and clinical pharmacists leads not only to rational administration of antibiotics, but also has a positive influence on treatment outcome. The gold standards for pathogen identification are still culture-based detection and microbiologic resistance testing for the various antibiotic groups. Despite the rapid investigation time, novel polymerase chain reaction(PCR)-based procedures for pathogen identification and resistance determination are currently only an adjunct to routine sepsis diagnostics, due to the limited number of studies, high costs, and limited availability. In complicated septic courses with multiple anti-infective therapies or recurrent sepsis, PCR-based procedures can be used in addition to treatment monitoring and diagnostics. Novel antibiotics represent potent alternatives in the treatment of MDR infections. Due to the often defined spectrum of pathogens and the practically (still) absent resistance, they are suitable for targeted treatment of severe MDR infections (therapy escalation). (Contribution available free of charge by "Free Access" [ https://link.springer.com/article/10.1007/s00101-017-0396-z ].).

MicroRNAs 143 and 150 in whole blood enable detection of T-cell immunoparalysis in sepsis.

BACKGROUND: Currently, no suitable clinical marker for detection of septic immunosuppression is available. We aimed at identifying microRNAs that could serve as biomarkers of T-cell mediated immunoparalysis in sepsis. METHODS: RNA was isolated from purified T-cells or from whole blood cells obtained from septic patients and healthy volunteers. Differentially regulated miRNAs were identified by miRNA Microarray (n = 7). Validation was performed via qPCR (n = 31). RESULTS: T-cells of septic patients revealed characteristics of immunosuppression: Pro-inflammatory miR-150 and miR-342 were downregulated, whereas anti-inflammatory miR-15a, miR-16, miR-93, miR-143, miR-223 and miR-424 were upregulated. Assessment of T-cell effector status showed significantly reduced mRNA-levels of IL2, IL7R and ICOS, and increased levels of IL4, IL10 and TGF-ß. The individual extent of immunosuppression differed markedly. MicroRNA-143, - 150 and - 223 independently indicated T-cell immunoparalysis and significantly correlated with patient's IL7R-/ICOS-expression and SOFA-scores. In whole blood, composed of innate and adaptive immune cells, both traits of immunosuppression and hyperinflammation were detected. Importantly, miR-143 and miR-150 - both predominantly expressed in T-cells - retained strong power of discrimination also in whole blood samples. CONCLUSIONS: These findings suggest miR-143 and miR-150 as promising markers for detection of T-cell immunosuppression in whole blood and may help to develop new approaches for miRNA-based diagnostic in sepsis.

[Non-beneficial therapy and emotional exhaustion in end-of-life care : Results of a survey among intensive care unit personnel]. / Übertherapie und emotionale Erschöpfung in der "end-of-life care" : Ergebnisse einer Mitarbeiterumfrage auf der Intensivstation.

BACKGROUND: End-of-life care (EOLC) in the intensive care unit (ICU) is becoming increasingly more common but ethical standards are compromised by growing economic pressure. It was previously found that perception of non-beneficial treatment (NBT) was independently associated with the core burnout dimension of emotional exhaustion. It is unknown whether factors of the work environment also play a role in the context of EOLC. OBJECTIVE: Is the working environment associated with perception of NBT or clinician burnout? MATERIAL AND METHODS: Physicians and nursing personnel from 11 German ICUs who took part in an international, longitudinal prospective observational study on EOLC in 2015-2016 were surveyed using validated instruments. Risk factors were obtained by multivariate multilevel analysis. RESULTS: The participation rate was 49.8% of personnel working in the ICU at the time of the survey. Overall, 325 nursing personnel, 91 residents and 26 consulting physicians participated. Nurses perceived NBT more frequently than physicians. Predictors for the perception of NBT were profession, collaboration in the EOLC context, excessively high workload (each p ≤ 0.001) and the numbers of weekend working days per month (p = 0.012). Protective factors against burnout included intensive care specialization (p = 0.001) and emotional support within the team (p ≤ 0.001), while emotional exhaustion through contact with relatives at the end of life and a high workload were both increased (each p ≤ 0.001). DISCUSSION: Using the example of EOLC, deficits in the work environment and stress factors were uncovered. Factors of the work environment are associated with perceived NBT. To reduce NBT and burnout, the quality of the work environment should be improved and intensive care specialization and emotional support within the team enhanced. Interprofessional decision-making among the ICU team and interprofessional collaboration should be improved by regular joint rounds and interprofessional case discussions. Mitigating stressful factors such as communication with relatives and high workload require allocation of respective resources.

Milk production and composition, and progeny performance in young ewes with high merit for rapid growth and muscle and fat accumulation.

In ewe lambs, acceleration of growth and accumulation of both muscle and fat leads to earlier sexual maturity and better reproductive performance. The next stage in the development of this theme is to test whether these aspects of growth in young ewes affect milk production in their first lactation and the growth of their first progeny. We studied 75 young Merino ewes that had known phenotypic values for depth of eye muscle (EMD) and fat (FAT), and known Australian Sheep Breeding Values for post-weaning weight (PWT) and depths of eye muscle (PEMD) and fat (PFAT). They lambed for the first time at 1 year of age. Their lambs were weighed weekly from birth to weaning at 10 weeks to determine live weight gain and weaning weight. Progeny birth weight was positively associated with live weight gain and weaning weight (P0.05). The PWT of the sire was positively associated with live weight gain (P0.05). The concentrations of fat, protein, lactose and total solids in the milk were not affected by the phenotype or genotype of the mothers or of the sires of the mothers, or by the sex of the progeny (P>0.05). We conclude that selection of young Merino ewes for better growth, and more rapid accumulation of muscle and fat, will lead to progeny that are heavier at birth, grow faster and are heavier at weaning. Moreover, milk production and composition do not seem to be affected by the genetic merit of the mother for post-weaning live weight or PEMD or PFAT. Therefore, Merino ewes can lamb at 1 year of age without affecting the production objectives of the Merino sheep industry.

Early immune anergy towards recall antigens and mitogens in patients at onset of septic shock.

The pathology of sepsis is typically characterized by an infection and excessive initial inflammation including a cytokine storm, followed by a state of immune suppression or paralysis. This classical view of a two peak kinetic immune response is currently controversially discussed. This study was a sub-study of the randomized clinical Trial SISPCT registered with www.clinicaltrials.gov (NCT00832039, Registration date: 29/01/2009). Blood samples from 76 patients with severe sepsis and septic shock were incubated for 48 h at 37 °C in vitro with bacterial or fungal recall-antigens or specific mitogen antigens within 24 hours of sepsis onset. Recall-antigen stimulation led to a severe dampening of normal cytokine release. This immunologic anergy was similarly observed after mitogen stimulation. Moreover, patients under hydrocortisone therapy or with lowered arterial oxygen tension had further reductions in cytokine levels upon B- and T-cell mitogen stimulation. This investigation reveals an early onset of immunoparalysis during sepsis. This immune incompetence in mounting an adequate response to further infections includes previously sensitized pathogens, as seen with recall-antigens. Also, the immune-suppressive role of hydrocortisone and low PaO2 is highlighted. Aside from early broad-spectrum antimicrobial therapy, our findings reinforce the need for maximal immunological support and protection against further infections at the onset of sepsis.

Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients (Part I): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017

OBJECTIVE: To update the 2008 consensus statements for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in adult and pediatric patients. PARTICIPANTS: A multispecialty task force of 16 international experts in Critical Care Medicine, endocrinology, and guideline methods, all of them members of the Society of Critical Care Medicine and/or the European Society of Intensive Care Medicine. DESIGN/METHODS: The recommendations were based on the summarized evidence from the 2008 document in addition to more recent findings from an updated systematic review of relevant studies from 2008 to 2017 and were formulated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The strength of each recommendation was classified as strong or conditional, and the quality of evidence was rated from high to very low based on factors including the individual study design, the risk of bias, the consistency of the results, and the directness and precision of the evidence. Recommendation approval required the agreement of at least 80% of the task force members. RESULTS: The task force was unable to reach agreement on a single test that can reliably diagnose CIRCI, although delta cortisol (change in baseline cortisol at 60 min of <9 µg/dl) after cosyntropin (250 µg) administration and a random plasma cortisol of <10 µg/dl may be used by clinicians. We suggest against using plasma free cortisol or salivary cortisol level over plasma total cortisol (conditional, very low quality of evidence). For treatment of specific conditions, we suggest using intravenous (IV) hydrocortisone <400 mg/day for ≥3 days at full dose in patients with septic shock that is not responsive to fluid and moderate- to high-dose vasopressor therapy (conditional, low quality of evidence). We suggest not using corticosteroids in adult patients with sepsis without shock (conditional recommendation, moderate quality of evidence). We suggest the use of IV methylprednisolone 1 mg/kg/day in patients with early moderate to severe acute respiratory distress syndrome (PaO2/FiO2 < 200 and within 14 days of onset) (conditional, moderate quality of evidence). Corticosteroids are not suggested for patients with major trauma (conditional, low quality of evidence). CONCLUSIONS: Evidence-based recommendations for the use of corticosteroids in critically ill patients with sepsis and septic shock, acute respiratory distress syndrome, and major trauma have been developed by a multispecialty task force.

[Bacterial sepsis : Diagnostics and calculated antibiotic therapy]. / Bakterielle Sepsis : Diagnostik und kalkulierte Antibiotikatherapie.

The mortality of patients with sepsis and septic shock is still unacceptably high. An effective antibiotic treatment within 1 h of recognition of sepsis is an important target of sepsis treatment. Delays lead to an increase in mortality; therefore, structured treatment concepts form a rational foundation, taking relevant diagnostic and treatment steps into consideration. In addition to the assumed focus and individual risks of each patient, local resistance patterns and specific problem pathogens must be taken into account for selection of anti-infection treatment. Many pathophysiological alterations influence the pharmacokinetics of antibiotics during sepsis. The principle of standard dosing should be abandoned and replaced by an individual treatment approach with stronger weighting of the pharmacokinetics/pharmacodynamics (PK/PD) index of the substance groups. Although this is not yet the clinical standard, prolonged (or continuous) infusion of beta-lactam antibiotics and therapeutic drug monitoring (TDM) can help to achieve defined PK targets. Prolonged infusion is sufficient without TDM but for continuous infusion TDM is basically necessary. A further argument for individual PK/PD-oriented antibiotic approaches is the increasing number of infections due to multidrug resistant pathogens (MDR) in the intensive care unit. For effective treatment antibiotic stewardship teams (ABS team) are becoming more established. Interdisciplinary cooperation of the ABS team with infectiologists, microbiologists and clinical pharmacists leads not only to a rational administration of antibiotics but also has a positive influence on the outcome. The gold standards for pathogen detection are still culture-based detection and microbiological resistance testing for the various antibiotic groups. Despite the rapid investigation time, novel polymerase chain reaction (PCR)-based procedures for pathogen identification and resistance determination, are currently only an adjunct to routine sepsis diagnostics due to the limited number of studies, high costs and limited availability. In complicated septic courses with multiple anti-infective treatment or recurrent sepsis, PCR-based procedures can be used in addition to therapy monitoring and diagnostics. Novel antibiotics represent potent alternatives in the treatment of MDR infections. Due to the often defined spectrum of pathogens and the practically absent resistance, they are suitable for targeted treatment of severe MDR infections (therapy escalation).

[International guidelines from the Surviving Sepsis Campaign : 2016 update]. / Internationale Leitlinien der Surviving Sepsis Campaign : Update 2016.

An update to the international guidelines for sepsis therapy was published by the Surviving Sepsis Campaign (SSC) in March 2017. The guidelines have been completely restructured and comprehensively deal with new evidence. The guidelines discuss sepsis-specific therapeutic measures and provide detailed recommendations on general intensive care measures for sepsis. This article summarizes the most important amendments and suggests delving deeper into the guidelines.

Relationships among Puberty, Muscle and Fat, and Liveweight Gain during Mating in Young Female Sheep.

Greater depths of muscle are associated with better reproductive performance in ewe lambs, but, in adult ewes, reproductive performance also seems to vary with liveweight gain during the mating period. Therefore, in a large field study with Merino ewe lambs, we tested whether the relationships among eye muscle depth (EMD), fat depth (FAT) and reproductive performance depend on liveweight gain during the mating period. We selected lambs with a wide range in phenotypic values for depths of eye muscle (EMD) and fat (FAT) and assigned them to dietary treatments designed to achieve low (LOW, n = 244) or high (HIGH, n = 237) rates of liveweight gain during a 28-day mating period. The LOW treatment maintained live weight, whereas the HIGH treatment gained 179 ± 3.8 g/day (p < 0.001). From those ewe lambs that attained puberty, first oestrus was detected at live weight 37.8 ± 0.2 kg and age 232 days. The proportion of ewes that attained puberty increased with EMD (p < 0.01). Ewes from the HIGH treatment were more fertile (pregnant ewes per 100 ewes exposed to rams) and had a higher reproductive rate (foetuses in utero per 100 ewes exposed to rams; p < 0.001) than those from the LOW treatment. Fertility and reproductive rate were positively correlated with weight gain during mating as well as live weight at the start of mating, FAT and EMD (p < 0.05 to <0.001). We conclude that faster growth, due to either extra nutrition during mating or higher phenotypic potential for fat and muscle, will increase reproductive performance in ewe lambs mated at 8 months of age.