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BACKGROUND Targeted temperature management is a standard therapy for unconscious survivors of cardiac arrest. To date, multiple cooling methods are available including invasive intravascular cooling devices (IVDs), which are widely used in the clinical setting. Recently, esophageal heat exchangers (EHEs) have been developed providing cooling via the esophagus that is located close to the aorta and inferior vena cava. The objective was to compare mean cooling rates, as well as differences, to target temperature during maintenance and the rewarming period of IVD and EHE. METHODS The study was conducted in 16 female domestic pigs. After randomization to either IVD or EHE (n = 8/group), core body temperature was reduced to 33°C. After 24 hours of maintenance (33°C), animals were rewarmed using a target rate of 0.25°C/h for 10 hours. All cooling phases were steered by a closed-loop feedback system between the internal jugular vein and the chiller. After euthanasia, laryngeal and esophageal tissue was harvested for histopathological examination. RESULTS Mean cooling rates (4.0°C/h ± 0.4°C/h for IVD and 2.4°C/h ± 0.3°C/h for EHE; P < .0008) and time to target temperature (85.1 ± 9.2 minutes for IVD and 142.0 ± 21.2 minutes for EHE; P = .0008) were different. Mean difference to target temperature during maintenance (0.07°C ± 0.05°C for IVD and 0.08°C ± 0.10°C for EHE; P = .496) and mean rewarming rates (0.2°C/h ± 0.1°C/h for IVD and 0.3°C/h ± 0.2°C/h for EHE; P = .226) were similar. Relevant laryngeal or esophageal tissue damage could not be detected. There were no significant differences in undesired side effects (eg, bradycardia or tachycardia, hypokalemia or hyperkalemia, hypoglycemia or hyperglycemia, hypotension, overcooling, or shivering). CONCLUSIONS After insertion, target temperatures could be reached faster by IVD compared to EHE. Cooling performance of IVD and EHE did not significantly differ in maintaining target temperature during a targeted temperature management process and in active rewarming protocols according to intensive care unit guidelines in this experimental setting.

With the coronavirus disease 2019 (COVID-19) outbreak hospitals prepared for increasing numbers of patients without knowing how patient populations were evolving and what resources would be required. The present study aimed to analyze the impact of the local COVID-19 pandemic on emergency resources of all hospitals in a major urban center (Mönchengladbach) in Germany.This observational multicenter study involved all acute care hospitals (n = 4). Systemic emergency department (ED) parameters from weeks 4-24 in 2020 were compared to the corresponding period in 2019 for each hospital and in a summative data analysis using a logistic regression model.The first regional COVID-19 patients were detected in week 9 of 2020. The cumulative number of ED visits dropped from 34,659 in 2019 to 28,008 in 2020. Weekly ED visits per hospital decreased from week 8 onwards between 38% and 48% per week and hospital and began to rise again after week 16. The pooled data analysis of ED patients showed significant decreases in outpatient visits (20,152 vs. 16,477, p 0.001), hospital admissions (14,507 vs. 11,531, p 0.001), and work-related accidents (2290 vs. 1468, p 0.001). The decrease in ED to ICU admissions showed no significance (2093 vs. 1566, p = 0.255). The decline in ED cases was equally distributed between the medical specialties.The regional COVID-19 outbreak led to significantly reduced ED contacts in a German major urban region after the first COVID-19 cases appeared. Both hospital admissions and the number of ED to ICU admissions decreased, whereas the ratio of emergency outpatients vs. inpatients remained stable. Therefore, it can be assumed that patients with severe medical problems did not seek emergency care. These secondary effects of the pandemic on healthcare and the socioeconomic impact should be analyzed further.HINTERGRUND: Zu Beginn der COVID-19-Pandemie im Jahr 2020 bereiteten sich das Gesundheitssystem und die Krankenhäuser in Deutschland auf höhere Patientenzahlen insgesamt und auch auf die Aufnahme zahlreicher kritisch kranker Patienten vor. Dazu mussten Ressourcen mobilisiert und Prozesse angepasst werden, die sowohl einem neuen Patientenkollektiv als auch der bisherigen Patientenversorgung gerecht werden sollten. Als eine der ersten deutschen Großstädte musste Mönchengladbach entsprechende Maßnahmen treffen, ohne dass die genauen Auswirkungen der Pandemie auf die Zusammensetzung der Patientenpopulationen abgeschätzt werden konnten bzw. bekannt war, ob ausreichend Notfallressourcen zur Verfügung stehen. In dieser Studie wird die Inanspruchnahme der kompletten Krankenhaus-Notfallstrukturen einer deutschen Großstadt zu Beginn der Corona-Pandemie analysiert.In dieser multizentrischen Observationsstudie aller (n = 4) Zentralen Notaufnahmen (ZNA) einer deutschen Großstadt (Mönchengladbach, ca. 274.000 Einwohner) wurde das Patientenaufkommen in den ZNA in den Kalenderwochen (KW) 4–24 im Jahr 2020 mit dem korrespondierenden Zeitraum (KW 4–24) in 2019 verglichen. Die weitere Auswertung erfolgte sowohl für jedes einzelne Krankenhaus als auch im kumulativen Gesamtvergleich in einer logistischen Regressionsanalyse. Aufgrund der voneinander unabhängigen Auswertungen der einzelnen Krankenhäuser wurde eine Bonferroni-Korrektur für das Signifikanzniveau durchgeführt.Die ersten regionalen COVID-19-Patienten wurden in Woche 9 des Jahres 2020 entdeckt. Die kumulative Anzahl der Patienten in der ZNA sank von 34.659 im Jahr 2019 auf 28.008 im Jahr 2020. Die wöchentliche Anzahl pro Krankenhaus nahm ab Woche 8 zwischen 38% und 48% pro Woche und Krankenhaus ab und begann nach Woche 16 wieder zu steigen. Die gepoolte Datenanalyse des Patientenaufkommens in der ZNA zeigte einen signifikanten Rückgang ambulanter Notfallpatienten (20.152 vs. 16.477; p 0,001), Notfallpatienten mit Bedarf zur stationären Behandlung (14.507 vs. 11.531; p 0,001) und der Arbeitsunfälle (2290 vs. 1468; p 0,001). Der Rückgang der Einweisungen von der Notaufnahme auf die Intensivstation zeigte keine Signifikanz (2093 vs. 1566; p = 0,255). Der Rückgang des Patientenaufkommens in den ZNA verteilte sich gleichmäßig auf die medizinischen Fachgebiete.Der regionale COVID-19-Ausbruch führte in einer deutschen Großstadtregion nach dem Auftreten der ersten COVID-19-Fälle zu einem deutlich reduzierten Patientenaufkommen in den ZNA. Auch die Zahl von stationären Aufnahmen und Intensivaufnahmen war rückläufig, während das Verhältnis von ambulanten Notfallpatienten zu stationären Patienten stabil blieb. Daher kann davon ausgegangen werden, dass Patienten mit schweren medizinischen Problemen keine Notfallversorgung aufgesucht haben. Diese sekundären Effekte der Pandemie auf das Gesundheitswesen und die sozioökonomischen Auswirkungen sollten weiter analysiert werden.

BACKGROUND The vascular endothelial glycocalyx is susceptible to ischemia and hypoxia. Released soluble components of the endothelial glycocalyx (EG) have been identified as potential damage associated molecular patterns (DAMPs) able to enhance an ongoing inflammatory response. Shedding of the EG has been associated with released atrial-natriuretic peptide (ANP) during cardiac surgery procedures. A novel hemoadsorption technique (CytoSorb®) has been shown to effectively remove molecules up to 55 kDa unspecifically from circulation. It is not known whether ANP or glycocalyx components can be removed successfully by this technique. METHODS In 15 patients undergoing on-pump cardiac surgery, the hemoadsorption device was integrated in the cardiopulmonary bypass (CPB) circuit. Pre- and post-adsorber concentrations of ANP, heparan sulphate (HEP), syndecan-1 (SYN) and hyaluronan (HYA) were measured at 10 (T1), 30 (T2), and 60 (T3) minutes after aortic cross-clamping and complete CPB. RESULTS Hemoadsorption significantly reduced mean HEP concentrations (-157.5 [333.4] ng/mL; P

Sağır, Özlem (Balikesir Author), Introduction More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. Methods and analysis EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. Ethics and dissemination EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369. ©

Background: The outbreak of the coronavirus disease 2019 (COVID-19) caused by the severe respiratory distress syndrome coronavirus 2 (SARS-CoV-2) led to severe disruption in social life and economics. The present study should analyze the impact of the local COVID-19 epidemic on emergency resources for all hospitals in a major urban center (Moenchengladbach, Germany). Methods: An observational multicenter study was performed involving all four acute care hospitals. Systemic parameters department (ED) parameters from week 4 to 24 in 2020 were compared to the corresponding period in 2019 for each hospital and in a summative data analysis using a logistic regression model. Outcomes: ED visits, ED to hospital admission, ED to Intensive Care Unit (ICU) admission, medical specialties of admitted patients, work related accidents. Results: In week 9/2020 the first SARS-CoV-2 positive patients were detected in our region. All hospitals decided to minimize elective admissions to ensure operational capability for COVID-19 patients. The summative number of ED visits dropped from 34,659 to 28,008. Numbers decreased from week 8 on between 38% and 48% per week per hospital at the maximum and began to rise again from week 16 on. The pooled data analysis showed statistically significant decreases in outpatient ED visits (20,152 vs. 16,477, p=Conclusion: The regional COVID-19 outbreak led to significantly reduced ED contacts after the first COVID-19 cases appeared. Even the admissions to the hospitals and the number of ED to ICU-admissions decreased, which is potentially dangerous, because the ratio of emergency outpatients vs. inpatients remained stable. Therefore, one can assume that patients with severe medical problems did not seek ED care in many cases. The decline of patients was earlier than in other German hospitals and in contrast to the findings in the U.S. and Italy where ED visits and hospital admissions in medical disciplines increased.

Background Peri-operative critical events are still a major problem in paediatric anaesthesia care. Access to more experienced healthcare teams might reduce the adverse event rate and improve outcomes. Objective The current study analysed incidences of peri-operative paediatric cardiac arrest before and after implementation of a specialised paediatric anaesthesia team and training programme. Design Retrospective cohort study with before-and-after analysis. Setting Department of Anaesthesiology and Intensive Care Medicine, University Hospital of Cologne, Germany. Patients A total of 36 243 paediatric anaesthetics (0 to 18 years) were administered between 2008 and 2016. Intervention Implementation of a specialised paediatric anaesthesia team and training programme occurred in 2014 This included hands-on supervised training in all fields of paediatric anaesthesia, double staffing for critical paediatric cases and a 24/7 emergency team. A logistic regression analysis with risk factors (age, ASA physical status, emergency) was used to evaluate the impact of implementation of the specialised paediatric anaesthesia team. Main outcome measures Incidences of peri-operative paediatric cardiac arrest and anaesthesia-attributable cardiac arrest before and after the intervention. Results Twelve of 25 paediatric cardiac arrests were classified as anaesthesia-attributable. The incidence of overall peri-operative paediatric cardiac arrest was 8.1/10 000 (95% CI 5.2 to 12.7) in the period 2008 to 2013 and decreased to 4.6/10 000 (95% CI 2.1 to 10.2) in 2014 to 2016. Likewise, the incidence of anaesthesia-attributable cardiac arrest was lower after 2013 [1.6/10 000 (95% CI 0.3 to 5.7) vs. 4.3/10 000 (95% CI 2.3 to 7.9)]. Using logistic regression, children anaesthetised after 2013 had nearly a 70% lower probability of anaesthesia-attributable cardiac arrest (odds ratio 0.306, 95% CI 0.067 to 1.397; P = 0.1263). For anaesthesia-attributable cardiac arrest, young age was the most contributory risk factor, whereas in overall paediatric cardiac arrest, ASA physical statuses 3 to 5 played a more important role. Conclusion In this study on incidences of peri-operative paediatric cardiac arrest from a European tertiary care university hospital, implementation of a specialised paediatric anaesthesia team and training programme was associated with lower incidences of peri-operative paediatric cardiac arrest and a reduced probability of anaesthesia-attributable cardiac arrest.

Zusammenfassung Hintergrund Im Jahr 2017 wurden weltweit etwa 4 Milliarden Menschen mit einem Flugzeug transportiert. Die International Air Transport Association (IATA) prognostiziert für Europa bis zum Jahr 2034 eine durchschnittliche jährliche Steigerung der Passagierzahlen von 2,7%. In der zivilen Luftfahrt treten Notfälle an Bord (sogenannte In-Flight Medical Emergencies, IFME) mit einer Häufigkeit von 1 pro 14 000 bis 1 pro 50 000 transportierte Passagiere auf. Belastbare Daten über die exakte Häufigkeit und Art von medizinischen Notfällen an Bord von Flugzeugen existieren nicht. Ein Herz-Kreislauf-Stillstand tritt statistisch gesehen nur in 0,3% der Notfälle an Bord auf. Dieses Ereignis ist jedoch mit einer Mortalität von 86% assoziiert und stellt daher Passagiere und Crew zugleich vor eine große Herausforderung. Mit der Leitlinie zum In-Flight Cardiac Arrest (IFCA) wurden 28 spezifische Empfehlungen erarbeitet. Ziel der Leitlinie war es, spezifische Handlungsempfehlungen für mitfliegende Ärzte, Kabinenpersonal (Cabin Crew) und auch Fluglinien zur Behandlung des Herz-Kreislauf-Stillstands an Bord von Luftfahrzeugen zu generieren.

BACKGROUND Education of schoolchildren in cardiopulmonary resuscitation (CPR) is a strategic goal for improvement of bystander CPR in society. OBJECTIVE(S) The primary objective was to analyse the impact of CPR training on the resuscitation knowledge and self-confidence of secondary schoolchildren. In addition, independent predictors of improved CPR knowledge and self-confidence were investigated. DESIGN Randomised-interventional controlled study. SETTING Four secondary schools in Germany. PARTICIPANTS Four hundred and twenty-four schoolchildren aged from 14 to 18 years were included into the study. Fifty-one percent were female, and 33% had an immigrant background. INTERVENTION The intervention group received a 90-min CPR training session, whereas controls had no intervention. Levels of knowledge and self-confidence in initiating CPR were analysed by a study questionnaire before (t0), 90 min after (t1) and 6 months after training (t2). MAIN OUTCOME MEASURES Based on the evaluation of study questionnaires, the primary endpoint was to determine the development of resuscitation knowledge and self-confidence in initiating cardiopulmonary resuscitation at survey time-points t0, t1 and t2. RESULTS Schoolchildren in the intervention group (n=207) showed a significantly higher level of knowledge (P

In recent decades, the incidences of anaesthesia-related perioperative mortality and adverse outcomes have decreased drastically. However, to date, data on perioperative cardiac arrest and risk factors of perioperative cardiac arrest from European countries are scarce.To determine the incidences of perioperative cardiac arrest and rates of anaesthesia-related and anaesthesia-contributory cardiac arrest. Identification of pre-existing risk factors leading to perioperative cardiac arrest.Retrospective cohort study.Department of Anaesthesiology and Intensive Care Medicine, University Hospital of Cologne, Germany.Perioperative critical incident reports between 2007 and 2012 were screened, and reports on cardiac arrest within 24 h postoperatively were identified. Cardiac arrests were classified as 'anaesthesia-related', 'anaesthesia-contributory' or 'anaesthesia-unrelated' by two reviewers independently. Univariate and multi-variate logistic regression analysis was used to identify risk factors associated with perioperative cardiac arrest.Analysis of 318 critical incidents from 169 500 anaesthetics revealed 99 perioperative cardiac arrests. This is an overall incidence of perioperative cardiac arrest of 5.8/10 000 anaesthetics [95% confidence interval (CI), 4.7 to 7.0]. The rate of anaesthesia-related cardiac arrest was 0.7/10 000 (95% CI, 0.3 to 1.1), and the rate of anaesthesia-contributory cardiac arrest was 1.7/10 000 (95% CI, 1.1 to 2.3). Most cardiac arrests related to anaesthesia were due to respiratory events. From the multi-variate analysis, American Society of Anesthesiologists physical status grade at least 3 [P = 0.007, odds ratio (OR) 2.59 (95% CI, 1.29 to 5.19)], emergency surgery [P 0.001, OR 4.00 (95% CI, 2.15 to 7.54)] and pre-existing cardiomyopathy [P 0.001, OR 17.48 (95% CI, 6.18 to 51.51)] emerged as predictors of cardiac arrest.These first available European data on perioperative cardiac arrest from a large unselected cohort indicate that the overall perioperative incidence of cardiac arrest at our institution was slightly lower than published in the literature, whereas rates of anaesthesia-related and anaesthesia-contributory cardiac arrest were comparable. Most cardiac arrests related to anaesthesia were due to respiratory events. American Society of Anesthesiologists physical status grade at least 3, emergency surgery and pre-existing cardiomyopathy appear to be relevant risk factors for cardiac arrest.

Cancer is one of the leading causes of death worldwide. New targeted and individualized therapies and drugs provide a survival benefit for an increasing number of patients, but can also cause severe side effects. An increasing number of oncology patients are admitted to intensive care units (ICU) because of cancer-related complications or treatment-associated side effects. Postoperative care, respiratory distress and sepsis are the leading causes for admission. Tumor mass syndromes and tumor lysis may require urgent treatment. Traditional anticancer chemotherapy is associated with infections and immunosuppression. Newer agents are generally well-tolerated and side effects are mild or moderate, but overwhelming inflammation and autoimmunity can also occur. Cellular treatment, such as with chimeric antigen receptor modified T‑cells, monoclonal and bispecific antibodies targeting immune effectors and tumor cells are associated with cytokine release syndrome (CRS) with hypotension, skin reactions and fever. It is related to excessively high levels of inflammatory cytokines. Immune checkpoint inhibitors can lead to immune-related adverse events (IRAEs), such as colitis and endocrine disorders. Noninfectious respiratory complications, such as pneumonitis can also occur. Recent studies revealed that short-term and medium-term survival of cancer patients is better than previously expected. In this review article we summarize diagnostic and treatment strategies for common life-threatening complications and emergencies requiring ICU admission. Furthermore, strategies for rational admission policies are presented.

Key Clinical Message Individual airway management is mandatory in patients with large goiters undergoing thyroid surgery. Preoperative endoscopic airway evaluation and imaging studies can support clinical decision making. Awake tracheotomy can be an effective and reasonable airway management strategy in such patients.

Pro Jahr reisen weltweit uber 3 Mrd. Menschen mit einem Luftfahrzeug. Bezogen auf die Anzahl transportierter Passagiere tritt ein medizinischer Notfall mit einer Haufigkeit von 1/14 000 bis 1/50 000 transportierten Passagieren auf. Der Herz-Kreislauf-Stillstand wahrend eines Fluges (in-flight cardiac arrest, IFCA) hat einen Anteil von 0,3 % an den Notfallen an Bord, besitzt aber andererseits eine Mortalitat von 86 %. Bisher existierte zum IFCA keine evidenzbasierte Leitlinie. Fur die Erstellung einer diesbezuglichen Leitlinie wurde eine Taskforce gegrundet, die publizierte Studien und die daraus abzuleitende Evidenz analysierte. Mittels systematischer Literaturanalyse und der Verwendung der Grade-, Rand- und Delphi-Methodik wurden spezifische Empfehlungen fur die Therapie des IFCA erstellt. Fur verschiedene Bereiche wurden spezifische Empfehlungen durch die Taskforce erarbeitet: Notfallausstattung an Bord, EKG, Reanimationstechniken, (Wiederholungs-)Training fur Besatzungen, Vorgehen nach „Return of Spontaneous Circulation“ (ROSC) und auserplanmasige Zwischenlandungen. Die Empfehlungen geben Arzten an Bord Hinweise, wie auf evidenzbasiertem Niveau mit IFCA-Patienten im Idealfall zu verfahren ist.

Thoracoabdominal esophageal resection for malignant disease is frequently associated with pulmonary infection. Whether prolonged antibiotic prophylaxis beyond a single perioperative dose is advantageous in preventing pulmonary infection after thoracoabdominal esophagectomy remains unclear. In this retrospective before-and-after analysis, 173 patients between January 2009 and December 2014 from a prospectively maintained database were included. We evaluated the effect of a 5-day postoperative course of moxifloxacin, which is a frequently used antimicrobial agent for pneumonia, on the incidence of pulmonary infection and mortality after thoracoabdominal esophagectomy. 104 patients received only perioperative antimicrobial prophylaxis (control group) and 69 additionally received a 5-day postoperative antibiotic therapy with moxifloxacin (prolonged-course). 22 (12.7%) of all patients developed pneumonia within the first 30 days after surgery. No statistically significant differences were seen between the prolonged group and control group in terms of pneumonia after 7 (p = 0.169) or 30 days (p = 0.133), detected bacterial species (all p > 0.291) and 30-day mortality (5.8 vs 10.6%, p = 0.274). A preemptive 5-day postoperative course of moxifloxacin does not reduce the incidence of pulmonary infection and does not improve mortality after thoracoabdominal esophagectomy.

Purpose of review The number of anaesthetic procedures in the ambulatory setting is steadily increasing. During the last years, more and more patients with complex medical conditions undergo ambulatory interventions. This review will focus on airway management practices, but especially on techniques used in the ambulatory setting. It will highlight recent literature published in the focus of ambulatory anaesthesia and will discuss relevant findings of the last year. Methods Literature search and analysis performed independently by two reviewers. Recent findings Practical points to improve success of anaesthesia and to avoid complications in the ambulatory setting are provided. In addition to concepts for the (un)expected difficult airway, new supraglottic devices, and modern concepts for teleconsultation, are discussed. Summary There are several points which should be considered for ambulatory anaesthesia. Selected patient groups (e.g., obstructive sleep apnoea, obesity) may have a higher anaesthesia-related risk. To handle the more and more complex conditions in a growing number of ambulatory patients, straightforward concepts, especially for the (un)expected difficult airway, are required.

By the end of the year 2016, approximately 3 billion people worldwide travelled by commercial air transport. Between 1 out of 14,000 and 1 out of 50,000 passengers will experience acute medical problems/emergencies during a flight (i.e., in-flight medical emergency). Cardiac arrest accounts for 0.3% of all in-flight medical emergencies. So far, no specific guideline exists for the management and treatment of in-flight cardiac arrest (IFCA). A task force with clinical and investigational expertise in aviation, aviation medicine, and emergency medicine was created to develop a consensus based on scientific evidence and compiled a guideline for the management and treatment of in-flight cardiac arrests. Using the GRADE, RAND, and DELPHI methods, a systematic literature search was performed in PubMed. Specific recommendations have been developed for the treatment of IFCA. A total of 29 specific recommendations for the treatment and management of in-flight cardiac arrests were generated. The main recommendations included emergency equipments as well as communication of the emergency. Training of the crew is of utmost importance, and should ideally have a focus on CPR in aircraft. The decision for a diversion should be considered very carefully.

Background In randomised controlled trials, procalcitonin (PCT)-guided antibiotic treatment has been proven to significantly reduce length of antibiotic therapy in intensive care unit (ICU) patients. However, concern was raised on low protocol adherence and high rates of overruling, and thus the value of PCT-guided treatment in real clinical life outside study conditions remains unclear. In this study, adherence to a PCT protocol to guide antibiotic treatment in patients with severe sepsis and septic shock was analysed. Methods From 2012 to 2014, surgical ICU patients with severe sepsis or septic shock were retrospectively screened for PCT measurement series appropriate to make treatment decisions on antibiotic therapy. We compared (1) patients with appropriate PCT measurement series to patients without appropriate series; (2) patients who reached the antibiotic stopping advice threshold (PCT

During the last years, proteomic studies have revealed several interesting findings in experimental sepsis models and septic patients. However, most studies investigated protein alterations only in single organs or in whole blood. To identify possible sepsis biomarkers and to evaluate the relationship between protein alteration in sepsis affected organs and blood, proteomics data from the heart, brain, liver, kidney, and serum were analysed. Using functional network analyses in combination with hierarchical cluster analysis, we found that protein regulation patterns in organ tissues as well as in serum are highly dynamic. In the tissue proteome, the main functions and pathways affected were the oxidoreductive activity, cell energy generation, or metabolism, whereas in the serum proteome, functions were associated with lipoproteins metabolism and, to a minor extent, with coagulation, inflammatory response, and organ regeneration. Proteins from network analyses of organ tissue did not correlate with statistically significantly regulated serum proteins or with predicted proteins of serum functions. In this study, the combination of proteomic network analyses with cluster analyses is introduced as an approach to deal with high-throughput proteomics data to evaluate the dynamics of protein regulation during sepsis.

To analyse antibiotic use density (AD)—World Health Organization defined daily doses/1,000 patient-days—before and after implementation of a local antimicrobial stewardship programme (ASP) in conjunction with a procalcitonin (PCT)-guided protocol in a surgical intensive care unit (ICU). In this retrospective observational study, data on 2,422 ICU patients between 2010 and 2012 were analysed. In 2011, an ASP in conjunction with a PCT protocol had been introduced into clinical practice. In a multivariate analysis, hospital mortality, length of stay (LOS) in hospital and ICU LOS were adjusted for effects from effective cost weight, gender, and age. AD and changes in the use of antibiotic classes were analysed. AD decreased from 1,005.0 in 2010 to 791.9 in 2012 which is a total reduction of 21.2 %. Consumption of aminoglycosides, cephalosporins and quinolones showed a marked reduction, whereas the use of penicillins did not change significantly. The multivariate models revealed no relevant changes in mortality rate, ICU LOS and hospital LOS. Implementation of an ASP in conjunction with a PCT protocol in 2011 was associated with a marked decrease in total AD and led to a significant change in the spectrum of antibiotics. Clinical outcomes appeared to remain unchanged over the study period.

Hypobaric hypoxia (HH) during airline travel induces several (patho-) physiological reactions in the human body. Whereas severe hypoxia is investigated thoroughly, very little is known about effects of moderate or short-term hypoxia, e.g. during airline flights. The aim of the present study was to analyse changes in serum protein expression and activation of signalling cascades in human volunteers staying for 30 min in a simulated altitude equivalent to airline travel. After approval of the local ethics committee, 10 participants were exposed to moderate hypoxia (simulation of 2400 m or 8000 ft for 30 min) in a hypobaric pressure chamber. Before and after hypobaric hypoxia, serum was drawn, centrifuged, and analysed by two-dimensional gel electrophoresis (2-DIGE) and matrix-assisted laser desorption/ionization followed by time-of-flight mass spectrometry (MALDI-TOF). Biological functions of regulated proteins were identified using functional network analysis (GeneMania®, STRING®, and Perseus® software). In participants, oxygen saturation decreased from 98.1 ± 1.3% to 89.2 ± 1.8% during HH. Expression of 14 spots (i.e., 10 proteins: ALB, PGK1, APOE, GAPDH, C1QA, C1QB, CAT, CA1, F2, and CLU) was significantly altered. Bioinformatic analysis revealed an association of the altered proteins with the signalling cascades "regulation of haemostasis" (four proteins), "metabolism" (five proteins), and "leukocyte mediated immune response" (five proteins). Even though hypobaric hypoxia was short and moderate (comparable to an airliner flight), analysis of protein expression in human subjects revealed an association to immune response, protein metabolism, and haemostasis.

The case of a young female patient with progressive chest trouble and dyspnea is reported. After development of a massive cerebral infarction, thrombolysis and afterwards decompressive craniectomy had to be performed. A patent foramen ovale (PFO) could be detected by transesophageal contrast-echocardiography accountable for a paradox embolism in existence with a deep vein thrombosis. The patient survived this situation but sustained persistent hemiparesis.

Summary Purpose Previous studies showed that pre-incisional administration of dextromethorphan (DM), a weak N-methyl-D-aspartic (NMDA) acid antagonist, reduces postoperative pain after epidural as well as general anesthesia. Aim of this study was therefore to proof the effects of DM on postoperative pain in patients undergoing orthopedic surgery under spinal anesthesia. Methods Forty-five patients undergoing elective orthopedic surgery were enrolled in this prospective, double-blinded and randomized study. Patients were randomly assigned to three groups (n = 15) and received either placebo or dextromethorphan (45 or 90 mg) p.o. Afterwards, a spinal catheter was inserted at the L2/3 or L3/4 interspace and spinal anesthesia with bupivacaine was induced and maintained at a level between Th 10 and Th 12. After completion of surgery patient controlled analgesia (PCA) with piritramide was started. Visual analogue pain scales (VAS) and analgesic requirements were assessed before surgery (control) as well as during the first 48 hours. Results The three groups were comparable with respect to biometric data, distribution of surgery as well as preoperative pain levels. VAS scores were not different between the three groups within 48 hours postoperatively. Furthermore, administration of pre-incisional DM had no influence on postoperative requirements of opioids (group D90: 59.5 ± 37.5 mg; group D45: 56.2 ± 37.1 mg piritramide; and group P: 49.3 ± 29.2 mg piritramide) within 48 hours. Conclusions In this study DM enables neither reduction of postoperative pain intensity nor analgesic- or opioid-sparing effects. Further studies to find out ideal dosage, way of administration and applicable kind of surgery should be implemented.

Administration of oxygen is one of the most common interventions in medicine. Previous research showed that differential regulated proteins could be linked to hyperoxia-associated signaling cascades in different tissues. However, it still remains unclear which signaling pathways are activated by hyperoxia. The present study analyses hyperoxia-induced protein alterations in lung, brain, and kidney tissue using a proteomic and bioinformatic approach. Pooled data of 36 Wistar rats exposed to hyperoxia were used. To identify possible hyperoxia biomarkers, and to evaluate the relationship between protein alterations in hyperoxia affected organs and blood, proteomics data from brain, lung, and kidney were analyzed. Functional network analyses (IPA&reg, PathwaysStudio&reg, and GENEmania&reg, ) in combination with hierarchical cluster analysis (Perseus&reg, ) was used to identify relevant pathways and key proteins. Data of 54 2D-gels with more than 2500 significantly regulated spots per gel were collected. Thirty-eight differentially expressed proteins were identified and consecutively analyzed by bioinformatic methods. Most differences between hyperoxia and normoxia (21 proteins up-regulated, 17 proteins down-regulated) were found immediately after hyperoxia (15 protein spots), followed by day 3 (13 spots), and day 7 (10 spots). A highly significant association with inflammation and the inflammatory response was found. Cell proliferation, oxidative stress, apoptosis and cell death as well as cellular functions were revealed to be affected. Three hours of hyperoxia resulted in significant alterations of protein expression in different organs (brain, lung, kidney) up to seven days after exposure. Further studies are required to interpret the relevance of protein alterations in signaling cascades during/after hyperoxia.

Recent studies have proposed roles for neurotrophins in the formation and plasticity of ocular dominance columns as well as in the regulation of dendritic arborization in visual cortex of higher mammals. To assess potential roles for neurotrophins in these processes, we have examined the developmental expression of BDNF and NT-3 mRNA in the cat's visual system using in situ hybridization. BDNF and NT-3 mRNAs are dynamically regulated in many CNS structures during embryonic and postnatal development, and both mRNAs undergo striking developmental changes in laminar specificity and levels of expression within primary visual cortex during the critical period for ocular dominance column formation. Within visual cortex, BDNF mRNA is found in neurons in deep cortical layers (5 and 6) prior to eye opening, and in both deep and superficial layers (2 and 3) shortly afterwards. Within layer 4, the target of thalamocortical axons, BDNF mRNA is low initially and rises to high levels by the end of the critical period for ocular dominance column formation. NT-3 mRNA is first detectable in small stellate neurons at the base of layer 4 (4c) after eye opening, and levels decrease near the end of the critical period. BDNF and NT-3 mRNAs can be detected in the lateral geniculate nucleus at birth, and levels peak during the critical period. In both structures, BDNF mRNA expression is maintained into adulthood, while NT-3 is undetectable in the adult. The presence and dynamic regulation of these neurotrophins in visual structures is consistent with suggested roles for both of these neurotrophins in axonal and dendritic remodeling known to accompany the formation of ocular dominance columns.

During the development of the visual system of higher mammals, axons from the lateral geniculate nucleus (LGN) become segregated into eye-specific patches (the ocular dominance columns) within their target, layer 4 of the primary visual cortex. This occurs as a consequence of activity-dependent synaptic competition between axons representing the two eyes. The possibility that this competition could be mediated through neurotrophin-receptor interactions was tested. Infusion of neurotrophin-4/5 (NT-4/5) or brain-derived neurotrophic factor (BDNF) into cat primary visual cortex inhibited column formation within the immediate vicinity of the infusion site but not elsewhere in the visual cortex. Infusion of nerve growth factor, neurotrophin 3 (NT-3), or vehicle solution did not affect column formation. These observations implicate TrkB, the common receptor for BDNF and NT-4/5, in the segregation of LGN axons into ocular dominance columns in layer 4. Moreover, they suggest that in addition to their better known roles in the prevention of cell death, neurotrophins may also mediate the activity-dependent control of axonal branching during development of the central nervous system.

Background Procalcitonin (PCT)-protocols to guide antibiotic treatment in severe infections are known to be effective. But less is known about the long-term effects of such protocols on antibiotic consumption under real life conditions. This retrospective study analyses the effects on antibiotic use in patients with severe sepsis and septic shock after implementation of a PCT-protocol. Methods We conducted a retrospective ICU-database search for adult patients between 2005 and 2009 with sepsis and organ dysfunction who where treated accordingly to a PCT-guided algorithm as follows: Daily measurements of PCT (BRAHMS PCT LIA®; BRAHMS Aktiengesellschaft, Hennigsdorf, Germany). Antibiotic therapy was discontinued if 1) clinical signs and symptoms of infection improved and PCT decreased to ≤1 ng/ml, or 2) if the PCT value was >1 ng/ml, but had dropped to 25-35% of the initial value within three days. The primary outcome parameters were: antibiotic days on ICU, ICU re-infection rate, 28-day mortality rate, length of stay (LOS) in ICU, mean antibiotic costs (per patient) and ventilation hours. Data from 141 patients were included in our study. Primary outcome parameters were analysed using covariance analyses (ANCOVA) to control for effects by gender, age, SAPS II, APACHE II and effective cost weight. Results From baseline data of 2005, duration of antibiotic therapy was reduced by an average of 1.0 day per year from 14.3 ±1.2 to 9.0 ±1.7 days in 2009 (p=0.02). ICU re-infection rate was decreased by yearly 35.1% (95% CI −53 to −8.5; p=0.014) just as ventilation hours by 42 hours per year (95% CI −72.6 to −11.4; p=0.008). ICU-LOS was reduced by 2.7 days per year (p

The case of a young female patient with progressive chest trouble and dyspnea is reported. After development of a massive cerebral infarction, thrombolysis and afterwards decompressive craniectomy had to be performed. A patent foramen ovale (PFO) could be detected by transesophageal contrast-echocardiography accountable for a paradox embolism in existence with a deep vein thrombosis. The patient survived this situation but sustained persistent hemiparesis.