[New challenges for intensive care medicine due to climate change and global warming]. / Neue intensivmedizinische Herausforderungen durch Klimawandel und globale Erderwärmung.

BACKGROUND: In the last five decades a continuous increase in the average global temperature has been recorded. Furthermore, natural disasters (e.g. heat waves, severe storms, floods and large forest fires) are becoming more frequent. The impact of global warming and climate change on health involves an increase in respiratory, cardiovascular, renal and cognitive mental diseases. Furthermore, a change in the frequency and patterns of infectious diseases can also be observed in Europe. MATERIAL AND METHODS: This article presents the most important studies that investigated diseases associated with the climate change, with special reference to those that represent a challenge for intensive care medicine. RESULTS: Currently available epidemiological data and statistical extrapolations indicate that diseases resulting from the climate change (acute infection-related respiratory and intestinal diseases, exacerbation of pre-existing pulmonary lesions, heat-related dehydration, cerebral insults and myocardial infarction) are relevant for intensive care medicine. Particular emphasis is placed on a significant increase in acute kidney damage during heat waves. A previously unknown pattern of infectious diseases necessitates new knowledge and targeted management. In some studies, persisting mental impairments were registered during heat waves and natural disasters, e.g. posttraumatic stress disorder. CONCLUSION: Intensive care medicine must be prepared for the challenges due to global warming and climate change. Slow but continuous changes (e.g. rise in temperature) as well as acute changes (e.g. heat waves and natural disasters) will induce an increased need for intensive medical care services (e.g. an increase in the need for renal replacement procedures). Intensive care physicians will need to be familiar with the diagnostics and management of diseases associated with the climate change. An initiative of the specialist societies involved would be welcomed.

[Update and Comment on the German S3 "Clinical Guideline for Treating Acute Respiratory Insufficiency with Invasive Ventilation and Extracorporeal Membrane Oxygenation: Evidence-Based Recommendations"]. / Was hat sich seit Publikation der S3-Leitlinie "Invasive Beatmung und Einsatz extrakorporaler Verfahren" getan?

In 2017 the German Clinical Guideline for Treating Acute Respiratory Insufficiency with Invasive Ventilation and Extracorporeal Membrane Oxygenation: Evidence-Based Recommendations were released. This article highlights emerging data and new concepts which were introduced since 2017. Among others it summarizes the current progress made in evidence-based recommendations of mechanical ventilation and extracorporeal membrane oxygenation (ECMO). In detail, the new evidence for treating severe ARDS with ECMO, phenotyping of ARDS, early neuromuscular blockade and the application of non-invasive ventilation and high-flow oxygen therapy are discussed.

[Health services research in intensive care medicine in Germany : Status quo and future challenges exemplified by acute pulmonary failure]. / Versorgungsforschung in der Intensivmedizin in Deutschland : Status quo und zukünftige Herausforderungen am Beispiel des akuten Lungenversagens.

Health services research (HSR) is a multidisciplinary field of research that describes disease treatment and health care and their framework conditions. In the last 20 years, the HSR aspect became more and more the clinical focus of intensive care medicine. Under this aspect HSR investigates the use of clinical measures and their impact on patient outcome under routine intensive care medical conditions. This article provides an overview of the current state of HSR in intensive care medicine in Germany using the example of acute respiratory distress syndrome (ARDS). The ARDS still represents a clinical disease with high intra-hospital mortality (30-60%) despite progress in intensive care medicine. Survivors of ARDS have substantial long-term limitations on physical and mental health. The treatment of ARDS patients is tedious, laborious for intensive care unit staff and complex. Despite evident treatment recommendations, these are only insufficiently implemented in the clinical routine. With the help of quality indicators, benchmarking, certification and peer review procedures, the quality of intensive care treatment in the clinical routine can be documented and improved. An important role in HSR is patient safety and focusing on the outcome with evaluation of the patient's will. As part of the establishment of the innovation fund for HSR, promising intensive medical care projects have been promoted to improve the quality of care and the quality of long-term outcome for intensive care patients. An important focus lies on the identification of factors that improve long-term quality of life after intensive care. The expansion of registries and telemedicine in intensive care offers the opportunity to bundle and share experiences more effectively and thereby establish (guideline-based) treatment recommendations faster in the clinical practice.

[Indications and limitations of ECMO therapy : Considerations on evidence, treatment decisions and ethical challenges]. / Indikationen und Grenzen der ECMO-Therapie : Überlegungen zur Evidenz, Therapieentscheidung und ethischen Herausforderung.

The present work sheds light on the possibilities and limitations of modern extracorporeal membrane oxygenation (ECMO) therapy in the case of heart or lung failure. Since the number of applications of extracorporeal lung and heart/lung replacement procedures has increased dramatically in the last few years in severely ill patients, decision-making for a meaningful indication and in the course of a possible therapy target change has become particularly difficult, especially with regard to the complex situation in organ transplantation in Germany. An attempt is made to elucidate the dilemma between data from large controlled trials and epidemiological studies and the patients' individuality.

[Impact of nursing staff shortage on intensive care medicine capacity in Germany]. / Auswirkungen des Pflegepersonalmangels auf die intensivmedizinische Versorgungskapazität in Deutschland.

BACKGROUND: Compared to other countries, Germany has the highest number of intensive care unit (ICU) beds, but, despite this, a shortage in ICU care is evident. Currently, little comprehensive data on ICU staffing and on subsequent closure of ICU beds are available. The current survey therefore aimed to systematically investigate the closure of ICU beds. METHOD: A survey was performed among authorized professional trainers in ICU medicine. RESULTS: Overall, a shortage of ICU beds following bed closure was evident in 76% of all ICU floors with 22% reporting daily ICU bed closure. In 47%, two ICU beds were not available. Emergency care was unrestricted in only 18%, while restrictions were reportedly frequent or even constant in 30%. The main reasons for ICU bed closure were the unavailability of ICU nurses (44%) and the co-existing unavailability of nurses and physicians (19%). On average, the nurse/patient ratio was 1:2.5 in the morning, 1:2.6 in the afternoon, and 1:3.1 in the night shift. CONCLUSIONS: ICU bed closure regularly occurs in Germany. The underlying main reason has been identified to be the unavailability of ICU nursing staff. This is suggested to directly interfere with emergency care. For this reason, an action plan is urgently needed.

[Influence of social characteristics on the duration of treatment, severity of the disease and social support of patients in a surgical intensive care unit]. / Einfluss sozialer Charakteristika auf die Behandlungsdauer, Erkrankungsschwere und soziale Unterstützung von Patienten einer operativen Intensivstation.

BACKGROUND: In critical illnesses low socioeconomic status (SES) is associated with higher morbidity and mortality. In addition to the SES, further factors at an individual level (e.g., sex, health insurance status and place of residence) may influence the severity of illness and medical treatment. We investigated these additional parameters in a secondary analysis of the ECSSTASI data. METHODS: Within the framework of the ECSSTASI study, 996 patients were recruited from a surgical intensive care unit. We examined the influence of sex, insurance status and place of residence on health-related behavior, disease severity, duration of intensive care and ventilation (28 ventilator-free days score, 28-VFDS) and social support by the next of kin. Multivariate-adjusted logistic regression analyses were carried out and odds ratios (OR) are presented with corresponding 95% confidence intervals. RESULTS: Among patients admitted to the intensive care unit, the disease severity (SOFA score >5) was significantly lower in women than in men (OR 0.62 [0.45-0.87]). Increasing size of the patient's town of residence was associated with a significantly shorter duration of treatment on the intensive care unit (OR 0.54 [0.32-0.91]). An increasing number of persons in the household was associated with a significantly increased risk of being ventilated longer compared to 1­person households (p = 0.028). Patients with private insurance (OR 1.87 [1.28-2.70]), patients from households with ≥4 persons (OR 1.92 [1.1-3.33]) and patients without German citizenship (OR 2.56 [1.39-4.55]) were visited significantly more often by next of kin. CONCLUSION: In addition to the SES, sociodemographic characteristics of the individual patient are associated with the course of treatment in intensive care medicine. The extent of social support by the next of kin depends on intercultural and individual patient characteristics. An increasing size of the town of residence and private health insurance status positively influence intensive care outcomes. In order to evaluate these data, further epidemiological studies in intensive care medicine are necessary.

The impact of venovenous extracorporeal membrane oxygenation on cytokine levels in patients with severe acute respiratory distress syndrome: a prospective, observational study.

OBJECTIVE: The immunoinflammatory response is central to the pathogenesis of acute respiratory distress syndrome (ARDS). However, little is known how this is affected by venovenous (VV) extracorporeal membrane oxygenation (ECMO). Our objective was to investigate the factors that influence the inflammatory response of patients with ARDS undergoing VV ECMO, and to analyse the impact of this response on hospital mortality. DESIGN AND SETTING: A prospective observational study of all consecutive patients with severe ARDS who had VV ECMO at a tertiary German ECMO centre from 2009 to 2015. Patients without complete datasets were excluded. Cytokines (interleukin [IL]6, IL8 and tissue necrosis factor [TNF]α) and inflammatory markers (white cell count and C-reactive protein) were assessed before ECMO initiation and on Days 1, 5 and 10, before explantation and at explantation. RESULTS: A total of 262 adult patients undergoing VV ECMO were analysed. Their median Sequential Organ Failure Assessment score was 12, PaO2/FiO2 ratio was 64 mmHg, and overall in-hospital mortality was 34%. Cytokine levels fell quickly within 24 hours and fell further over the first 5 days. Extra-pulmonary ARDS was associated with higher IL6 and IL8 levels compared with pulmonary ARDS. Mechanical ventilation with positive end-expiratory pressure ≥ 15 cmH2O before ECMO was associated with higher IL6, IL8 and TNFα levels. Driving pressures ≥ 19 cmH2O before ECMO were associated with higher IL8 levels. Non-survivors had higher IL6 and IL8 levels for the duration of ECMO. CONCLUSION: Cytokine levels, on average, fall rapidly after initiation of VV ECMO, which may be related to the reduction of invasiveness of mechanical ventilation. Higher cytokine levels are associated with extrapulmonary causes of ARDS, more aggressive mechanical ventilation before VV ECMO, and mortality.

[Life after ARDS]. / Das Leben nach ARDS.

Patients who survive acute respiratory distress syndrome (ARDS) often suffer from long-term physical and psychological sequelae. Lung function is commonly only mildly reduced, whereas general physical activity and walking distance are often compromised. Most markedly, these patients have a high incidence of depression, anxiety, and posttraumatic stress disorder. The rate of cognitive dysfunction is as high as 70-100% at the time of hospital discharge, and remains 46-80% and 20% one year and five years post discharge, respectively. The possibility of returning to work is markedly limited. Because of these outcomes, preventative strategies must be identified to reduce the high prevalence of physical and psychological morbidity. Prevention and treatment of delirium as well as early and consequent mobilization and intensive care unit diaries are potentially beneficial.

[Extracorporeal CO2 removal as an alternative to tracheotomy in a patient with extubation failure]. / Extrakorporale CO2-Elimination als Alternative zur Tracheotomie bei Weaningversagen.

We report a patient with chest trauma who was admitted to the ICU after surgery. As he fulfilled protocol-based criteria, he was extubated 7 days after admission. However, despite intermittent non-invasive ventilation, the patient had to be re-intubated on day 10 owing to progressive hypercapnia. We decided to support the patient with a mid-flow veno-venous extracorporeal carbon dioxide removal (ECCO2­R) system instead of a tracheotomy. Sufficient CO2 removal was established with a blood flow of 1.5 l/min and the patient was successfully extubated within a few hours. After 5 days of ECCO2­R the patient could be weaned and transferred to a general ward in a stable condition.

[Positioning therapy and early mobilization in intensive care units : Findings from the current 2015 guidelines]. / Lagerungstherapie und Frühmobilisation auf der Intensivstation : Erkenntnisse aus der aktuellen Leitlinie 2015.

The 2007 guidelines "Positioning for prophylaxis and therapy of pulmonary disorders" were completely revised in 2015 on behalf of the German Society of Anaesthesiology and Intensive Care Medicine. With regard to practical and scientific relevance, early mobilization of patients in critical care has been included in the guidelines for the first time. Furthermore, the recommendations for prone positioning have been updated, based on current evidence in medicine and nursing. In addition, recommendations regarding unsuitable positions that may actually harm patients were made. As such, the flat supine position should only be used in cases of urgent medical or nursing needs. This underlines the importance of a moderately elevated head of bed position (20(o)-45(o)) in mechanically ventilated patients.

Experts' opinion on management of hemodynamics in ARDS patients: focus on the effects of mechanical ventilation.

RATIONALE: Acute respiratory distress syndrome (ARDS) is frequently associated with hemodynamic instability which appears as the main factor associated with mortality. Shock is driven by pulmonary hypertension, deleterious effects of mechanical ventilation (MV) on right ventricular (RV) function, and associated-sepsis. Hemodynamic effects of ventilation are due to changes in pleural pressure (Ppl) and changes in transpulmonary pressure (TP). TP affects RV afterload, whereas changes in Ppl affect venous return. Tidal forces and positive end-expiratory pressure (PEEP) increase pulmonary vascular resistance (PVR) in direct proportion to their effects on mean airway pressure (mPaw). The acutely injured lung has a reduced capacity to accommodate flowing blood and increases of blood flow accentuate fluid filtration. The dynamics of vascular pressure may contribute to ventilator-induced injury (VILI). In order to optimize perfusion, improve gas exchange, and minimize VILI risk, monitoring hemodynamics is important. RESULTS: During passive ventilation pulse pressure variations are a predictor of fluid responsiveness when conditions to ensure its validity are observed, but may also reflect afterload effects of MV. Central venous pressure can be helpful to monitor the response of RV function to treatment. Echocardiography is suitable to visualize the RV and to detect acute cor pulmonale (ACP), which occurs in 20-25 % of cases. Inserting a pulmonary artery catheter may be useful to measure/calculate pulmonary artery pressure, pulmonary and systemic vascular resistance, and cardiac output. These last two indexes may be misleading, however, in cases of West zones 2 or 1 and tricuspid regurgitation associated with RV dilatation. Transpulmonary thermodilution may be useful to evaluate extravascular lung water and the pulmonary vascular permeability index. To ensure adequate intravascular volume is the first goal of hemodynamic support in patients with shock. The benefit and risk balance of fluid expansion has to be carefully evaluated since it may improve systemic perfusion but also may decrease ventilator-free days, increase pulmonary edema, and promote RV failure. ACP can be prevented or treated by applying RV protective MV (low driving pressure, limited hypercapnia, PEEP adapted to lung recruitability) and by prone positioning. In cases of shock that do not respond to intravascular fluid administration, norepinephrine infusion and vasodilators inhalation may improve RV function. Extracorporeal membrane oxygenation (ECMO) has the potential to be the cause of, as well as a remedy for, hemodynamic problems. Continuous thermodilution-based and pulse contour analysis-based cardiac output monitoring are not recommended in patients treated with ECMO, since the results are frequently inaccurate. Extracorporeal CO2 removal, which could have the capability to reduce hypercapnia/acidosis-induced ACP, cannot currently be recommended because of the lack of sufficient data.

Applicability of avidin protein coated mesoporous silica nanoparticles as drug carriers in the lung.

Mesoporous silica nanoparticles (MSNs) exhibit unique drug delivery properties and are thus considered as promising candidates for next generation nano-medicines. In particular, inhalation into the lungs represents a direct, non-invasive delivery route for treating lung disease. To assess MSN biocompatibility in the lung, we investigated the bioresponse of avidin-coated MSNs (MSN-AVI), as well as aminated (uncoated) MSNs, after direct application into the lungs of mice. We quantified MSN distribution, clearance rate, cell-specific uptake, and inflammatory responses to MSNs within one week after instillation. We show that amine-functionalized (MSN-NH2) particles are not taken up by lung epithelial cells, but induced a prolonged inflammatory response in the lung and macrophage cell death. In contrast, MSN-AVI co-localized with alveolar epithelial type 1 and type 2 cells in the lung in the absence of sustained inflammatory responses or cell death, and showed preferential epithelial cell uptake in in vitro co-cultures. Further, MSN-AVI particles demonstrated uniform particle distribution in mouse lungs and slow clearance rates. Thus, we provide evidence that avidin functionalized MSNs (MSN-AVI) have the potential to serve as versatile biocompatible drug carriers for lung-specific drug delivery.

[The challenge of acute kidney injury : Cross-sectional study on prevalence and costs in a university intensive care unit]. / Die Herausforderung akute Nierenschädigung : Querschnittsstudie zu Prävalenz und Kosten auf einer universitären Intensivstation.

BACKGROUND AND OBJECTIVES: The prognosis of intensive care patients with acute kidney injury (AKI), which is associated with increased mortality is still poor. Current data on the prevalence and the resulting costs of AKI and an overview of the most common diagnoses associated with AKI in German intensive care units (ICU) are lacking. PATIENTS AND METHODS: In this retrospective study all adult admissions (> 18 Jahre) in the five ICUs at the University Clinic Regensburg (in total 78 beds) from1 January 2011 to 31 December 2013 were evaluated. The ICU diagnoses commonly associated with AKI were identified using the international classification of diseases 10 (ICD 10). The length of ICU and hospital stays and AKI-associated hospital costs in the diagnosis-related groups (DRG) based reimbursement system were compared. RESULTS: A total of 891 ICU patients with AKI were classified according to the ICD 10 code. Acute respiratory distress syndrome (ARDS), myocardial infarction (MI) and sepsis were the three most common ICU conditions associated with AKI. A total of 1103 patients were admitted with 1 of these 3 main diagnoses and 249 (22.6 %) of these patients developed AKI. Patients with AKI had significantly longer mean ICU and hospital stays compared to patients without AKI (18.6 vs 5.1 days and 23.8 vs. 10.4 days, respectively, p < 0.001). The presence of AKI in critically ill patients with ARDS, MI and sepsis resulted in additional costs of 2,019,120.42 € at the University Hospital of Regensburg in 2013. CONCLUSION: Acute kidney injury in critically ill patients represents a significant medical and socioeconomic burden. Early recognition of patients at risk, coordinated research into novel interventions and establishment of the National Acute Kidney Injury Network for implementation of evidence-based therapies may be the next steps to decrease the incidence and severity of AKI and save costs for the national healthcare system.

A molecular nanocap activated by superparamagnetic heating for externally stimulated cargo release.

A novel thermoresponsive snaptop for stimulated cargo release from superparamagnetic iron oxide core - mesoporous silica shell nanoparticles based on a [2 + 4] cycloreversion reaction (retro-Diels Alder reaction) is presented. The non-invasive external actuation through alternating magnetic fields makes this material a promising candidate for future applications in externally triggered drug delivery.

[Short version S2e guidelines: "Positioning therapy and early mobilization for prophylaxis or therapy of pulmonary function disorders"]. / Kurzversion S2e-Leitlinie - "Lagerungstherapie und Frühmobilisation zur Prophylaxe oder Therapie von pulmonalen Funktionsstörungen".

The German Society of Anesthesiology and Intensive Care Medicine (DGAI) commissioned a revision of the S2 guidelines on "positioning therapy for prophylaxis or therapy of pulmonary function disorders" from 2008. Because of the increasing clinical and scientific relevance the guidelines were extended to include the issue of "early mobilization" and the following main topics are therefore included: use of positioning therapy and early mobilization for prophylaxis and therapy of pulmonary function disorders, undesired effects and complications of positioning therapy and early mobilization as well as practical aspects of the use of positioning therapy and early mobilization. These guidelines are the result of a systematic literature search and the subsequent critical evaluation of the evidence with scientific methods. The methodological approach for the process of development of the guidelines followed the requirements of evidence-based medicine, as defined as the standard by the Association of the Scientific Medical Societies in Germany. Recently published articles after 2005 were examined with respect to positioning therapy and the recently accepted aspect of early mobilization incorporates all literature published up to June 2014.

[Intercultural competence. Management of foreignness in intensive care medicine]. / Interkulturelle Kompetenz. Umgang mit Fremdheit in der Intensivmedizin.

BACKGROUND: Living in a multicultural society is characterized by different attitudes caused by a variety of religions and cultures. In intensive care medicine such a variety of cultural aspects with respect to pain, shame, bodiliness, dying and death is of importance in this scenario. AIM: To assess the importance of cultural and religious attitudes in the face of foreignness in intensive care medicine and nursing. Notification of misunderstandings and misinterpretations in communication and actions. MATERIAL AND METHODS: An analysis of the scientific literature was carried out and typical intercultural conflict burden situations regarding the management of brain death, organ donation and end of life decisions are depicted. RESULTS: Specific attitudes are found in various religions or cultures regarding the change of a therapeutic target, the value of the patient's living will and the organization of rituals for dying. Intercultural conflicts are mostly due to misunderstandings, assessment differences, discrimination and differences in values. CONCLUSION: Intercultural competence is crucial in intensive care medicine and includes knowledge of social and cultural influences of different attitudes on health and illness, the abstraction from own attitudes and the acceptance of other or foreign attitudes.

Factors of tidal volume variation during augmented spontaneous ventilation in patients on extracorporeal carbon dioxide removal. A multivariate analysis.

BACKGROUND: Extracorporeal carbon dioxide removal (ECCO2-R) allows lung protective ventilation using lower tidal volumes (VT) in patients with acute respiratory failure. The dynamics of spontaneous ventilation under ECCO2-R has not been described previously. This retrospective multivariable analysis examines VT patterns and investigates the factors that influence VT, in particular sweep gas flow and blood flow through the artificial membrane. METHODS: We assessed VT, respiratory rate (RR), minute ventilation (MV), and levels of pressure support (0-24 cm H2O), sweep gas flow (0-14 L/min) and blood flow through the membrane (0.8-1.8 L/min) in 40 patients from the moment they were allowed to breathe spontaneously. Modest hypercapnia was accepted. RESULTS: Patients tolerated moderate hypercapnia well. In a generalized linear model the increase in sweep gas flow (P<0.001), a low PaCO2 (P=0.029), and an increased breathing frequency (P<0.001) were associated with lower VT. Neither blood flow through the membrane (P=0.351) nor the level of pressure support (P=0.595) influenced VT size. CONCLUSION: Higher sweep gas flow is associated with low VT in patients on extracorporeal lung assist and augmented spontaneous ventilation. Such a technique can be used for prolonged lung protective ventilation even in the patient's recovery period.