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IMPORTANCE: Although current guidelines suggest the use of regional citrate anticoagulation (which involves the addition of a citrate solution to the blood before the filter of the extracorporeal dialysis circuit) as first-line treatment for continuous kidney replacement therapy in critically ill patients, the evidence for this recommendation is based on few clinical trials and meta-analyses. OBJECTIVE: To determine the effect of regional citrate anticoagulation, compared with systemic heparin anticoagulation, on filter life span and mortality. DESIGN, SETTING, AND PARTICIPANTS: A parallel-group, randomized multicenter clinical trial in 26 centers across Germany was conducted between March 2016 and December 2018 (final date of follow-up, January 21, 2020). The trial was terminated early after 596 critically ill patients with severe acute kidney injury or clinical indications for initiation of kidney replacement therapy had been enrolled. INTERVENTIONS: Patients were randomized to receive either regional citrate anticoagulation (n = 300), which consisted of a target ionized calcium level of 1.0 to 1.40 mg/dL, or systemic heparin anticoagulation (n = 296), which consisted of a target activated partial thromboplastin time of 45 to 60 seconds, for continuous kidney replacement therapy. MAIN OUTCOMES AND MEASURES: Coprimary outcomes were filter life span and 90-day mortality. Secondary end points included bleeding complications and new infections. RESULTS: Among 638 patients randomized, 596 (93.4%) (mean age, 67.5 years; 183 [30.7%] women) completed the trial. In the regional citrate group vs systemic heparin group, median filter life span was 47 hours (interquartile range [IQR], 19-70 hours) vs 26 hours (IQR, 12-51 hours) (difference, 15 hours [95% CI, 11 to 20 hours]; P

Introduction: The NLRP3 inflammasome is a key factor in innate immunity and plays a pivotal role in driving acute lung injury via IL-1β and IL-18. Recent studies highlighted the immunomodulatory effects of tetracyclines (TET) in the treatment of inflammatory diseases and identified inhibition of NLRP3 inflammsome as a potential mechanism. Aim: We investigated in a murine model whether TET reduces NLRP3 inflammasome-mediated lung inflammation and improves outcome. Methods: Mice were challenged with LPS i.t. and treated by i.p. injection of TET from d 0 for 10 d. Lung injury was determined by measurement of i) albumin concentration by ELISA, ii) neutrophil population by flow cytometry (both in BALF) and iii) histopathology. Concentration of IL-1β, IL-6, IL-18 and TNFα was measured by multiplex assay in BALF. The effect of TET on NLRP3 inflammasome was tested in BMDMs after stimulation with LPS plus nigericin. Concentration of IL-1β and TNFα was determined by ELISA and cleavage of caspase-1 via western blot. Results: TET treated mice showed significantly reduced weight loss and mortality (43% vs. 7%) compared to PBS treated animals. TET treatment diminished lung injury in terms of lower albumin (325±35 vs 144±16µg/ml) concentration and number of neutrophils. Histopathology showed reduced lung injury in TET-treated animals. TET decreased exclusively the concentration of IL-1β (152±16 vs 86±8 pg/ml) and IL-18 in BALF. TET selectively inhibited IL-1β secretion and caspase-1 activation after NLRP3 stimulation. Conclusions: Current study demonstrates that TET reduces acute lung injury in mice via inhibiting NLRP3 inflammasome activation, thereby reducing morbidity and mortality.

Photoelectron spectroscopy of microjets expanded into vacuum allows access to orbital energies for solute or solvent molecules in the liquid phase. Microjets of water, acetonitrile and alcohols have previously been studied; however, it has been unclear whether jets of low temperature molecular solvents could be realized. Here we demonstrate a stable 20 μm jet of liquid ammonia (-60 °C) in a vacuum, which we use to record both valence and core-level band photoelectron spectra using soft X-ray synchrotron radiation. Significant shifts from isolated ammonia in the gas-phase are observed, as is the liquid-phase photoelectron angular anisotropy. Comparisons with spectra of ammonia in clusters and the solid phase, as well as spectra for water in various phases potentially reveal how hydrogen bonding is reflected in the condensed phase electronic structure.

Heparine gelten im Rahmen der stationaren und zunehmend auch ambulanten Thromboseprophylaxe seit Jahrzehnten als Standardtherapie. Neben dem therapeutischen Nutzen birgt die Therapie mit Heparinen allerdings auch die Gefahr unerwunschter Nebenwirkungen wie Blutungen und Thrombozytopenien. Als schwerwiegende Nebenwirkung gilt die heparininduzierte Thrombozytopenie (HIT II). Die folgende Arbeit unterzieht die HIT II einer medizinokonomischen Betrachtung (Behandlung, Arzneimittel, Folgekosten aufgrund moglicher Komplikationen) und betrachtet im Hinblick auf eine mogliche HIT-II-Prophylaxe auch Aspekte der zunehmend im Fokus stehenden Patientensicherheit. Im Rahmen einer Literaturrecherche wurden die fur eine HIT-II-Behandlung zugelassenen Wirkstoffe Argatroban und Danaparoid evaluiert. Eine HIT II – insbesondere in Kombination mit thromboembolischen Komplikationen – bedeutet fur das Krankenhaus eine medizinokonomische Belastung. Zwar stellt dies nur eine Orientierungshilfe dar, zeigt aber auf, dass ein HIT-II-Syndrom nicht ausreichend durch das DRG-Entgeltsystem kostendeckend abgebildet wird. Eine fruhzeitige Thromboseprophylaxe mit Argatroban/Danaparoid bei HIT-II-Risikopatienten ist daher aus medizinokonomischen, aber auch aus patientensicherheitsrelevanten Gesichtspunkten in Erwagung zu ziehen. Erfahrungsgemas sollte bei diesen „medical needed“-Produkten (Antikoagulanzien) eine Arzneimittelversorgung aus Grunden der Patientensicherheit gewahrleistet sein. Das Risiko einer immunologischen Reaktion auf eine Heparintherapie ist bekannt. Im Sinne einer erhohten Patientensicherheit sollte die Thromboseprophylaxe mit einer risikoadjustierten HIT-II-Prophylaxe erfolgen.

INTRODUCTION: The aim of the EuReCa ONE study was to determine the incidence, process, and outcome for out of hospital cardiac arrest (OHCA) throughout Europe.METHODS: This was an international, pr ...

Hintergrund Auch wenn neuere Erkenntnisse zeigen, dass die routinemasige Anwendung mechanischer Reanimationshilfen beim auserklinischen Kreislaufstillstand keinen Vorteil zeigen, haben derartige Gerate in den letzten Jahren dennoch eine weite Verbreitung im Rettungsdienst gefunden.

Recently, we determined the detailed energy level structure of the $X^1\Sigma^+$, $A^1\Pi$ and $a^3\Pi$ states of AlF that are relevant to laser cooling and trapping experiments. Here, we investigate the $b^3\Sigma^+, v=0$ state of the AlF molecule. A rotationally-resolved (1+2)-REMPI spectrum of the $b^3\Sigma^+, v'=0 \leftarrow a^3\Pi, v''=0$ band is presented and the lifetime of the $b^3\Sigma^+, v=0$ state is measured to be 190(2)~ns. Hyperfine-resolved, laser-induced fluorescence spectra of the $b^3\Sigma^+, v'=0 \leftarrow X^1\Sigma^+, v''=1$ and the $b^3\Sigma^+, v'=0 \leftarrow a^3\Pi, v''=0$ bands are recorded to determine fine- and hyperfine structure parameters. The interaction between the $b^3\Sigma^+, v=0$ and the nearby $A^1\Pi$ state is studied and the magnitude of the spin-orbit coupling between the two electronic states is derived using three independent methods to give a consistent value of 10(1)~cm$^{-1}$. The triplet character of the $A$ state causes an $A\rightarrow a$ loss from the main $A-X$ laser cooling cycle below the 10$^{-6}$ level., Comment: 22 pages, 8 figures

Checklist – On site evaluation prior to ECMO. ECMO therapy protocol. ECMO debriefing protocol. STROBE Checklist for cohort studies (PDF 899 kb)

Der innerklinische Notfall ist eine Herausforderung fur das Risikomanagement im Krankenhaus. Zeitverzogerungen bei der Erkennung und Behandlung des kritisch kranken Patienten fuhren zu schwerwiegenden Zwischenfallen bis hin zum Kreislaufstillstand. Die Vermeidung unerwunschter Ereignisse und eine adaquate Reaktion im Notfall sind essenziell fur die Patientensicherheit. Es obliegt der Verantwortung der Krankenhausleitung, entsprechende Strukturen an die lokalen Gegebenheiten sowie Bedurfnisse anzupassen und zu etablieren. Neben der dem Krankheitszustand des Patienten angemessenen Uberwachung und der Einfuhrung von Fruherkennungssystemen bildet das MET dabei eine wichtige Saule im Kontext eines praventiven innerklinischen Notfallmanagementkonzeptes. Dabei bedarf es standardisierter praventiver Alarmierungskriterien.

Krankenhauser aller Versorgungsstufen konnen grundsatzlich von der Einfuhrung eines praventiven MET-Konzeptes zur fruhzeitigen Identifikation und Versorgung kritisch Kranker profitieren. Dafur muss das MET-System jeweils an die lokalen Strukturen und Anforderungen einer Klinik angepasst sein. Es bedarf struktureller und organisatorischer Veranderungen, deren Auspragung stark von soziologischen, kulturellen und politischen Gegebenheiten des Gesundheits- und Krankenhauswesens beeinflusst werden. Der Weg zur flachendeckenden Etablierung eines MET-Systems fuhrt uber eine erfolgreiche Integration und Beteiligung aller Berufsgruppen und Fachdisziplinen des Krankenhauses. Es ist ein Prozess des Umdenkens, des kulturellen Wandels notwendig, begleitet von Schulungsmasnahmen und einer Standardisierung der Verhaltensweise zur rechtzeitigen Erkennung des kritisch kranken Patienten.

Here we report on spectroscopic measurements of the aluminum monofluoride molecule (AlF; boson) that are relevant to laser cooling and trapping experiments. We measure the detailed energy-level structure of AlF in the X1Σ+ electronic ground state, in the A1Π state, and in the metastable a3Π state. We determine the rotational, vibrational, and electronic branching ratios from the A1Π state. We also study how the rotational levels split and shift in external electric and magnetic fields. We find that AlF is an excellent candidate for laser cooling on any Q line of the A1Π - X1Σ+ transition and for trapping at high densities. The energy levels in the X1Σ+,v=0 state and within each Ω manifold in the a3Π,v=0 state are determined with a relative accuracy of a few kHz, using laser-radio-frequency multiple resonance and ionization detection schemes in a jet-cooled, pulsed molecular beam. To determine the hyperfine and Λ-doubling parameters we measure transitions throughout the 0.1-MHz–66-GHz range, between rotational levels in the X1Σ+,v=0 state, and between rotational and Λ-doublet levels in all three spin-orbit manifolds of the a3Π,v=0 state. We measure the hyperfine splitting in the A1Π state using continuous wave (cw) laser-induced fluorescence spectroscopy of the A1Π,v=0←X1Σ+,v′′=0 band. The resolution is limited by the short radiative lifetime of the A1Π,v=0 state, which we experimentally determine to be 1.90±0.03 ns. The hyperfine mixing of the lowest rotational levels in the A1Π state causes a small loss from the main laser cooling transition of 10-5. The off-diagonal vibrational branching from the A1Π,v=0 state is measured to be (5.60±0.02)×10-3 in good agreement with theoretical predictions. The strength of the spin-forbidden A1Π,v=0→a3Π,v′=0 transition is measured to be seven orders of magnitude lower than the strength of the A1Π,v=0→X1Σ+,v′′=0 transition. We determine the electric dipole moments μ(X)=1.515±0.004 Debye, μ(a)=1.780±0.003 Debye and μ(A)=1.45±0.02 Debye in X1Σ+, v=0, a3Π,v=0 and A1Π,v=0, respectively, by recording cw laser excitation spectra in electric fields up to 150 kV/cm.

Sepsis, a life threating syndrome characterized by organ failure after infection, is the most common cause of death in hospitalized patients. The treatment of sepsis is generally supportive in nature, involving the administration of intravenous fluids, vasoactive substances and oxygen plus antibiotics to eliminate the pathogen. No drugs have been approved specifically for the treatment of sepsis, and clinical trials of potential therapies have failed to reduce mortality - suggesting that new approaches are needed. Abnormalities in the immune response elicited by the pathogen, ranging from excessive inflammation to immunosuppression, contribute to disease pathogenesis. Although hundreds of immunomodulatory agents are potentially available, it remains unclear which patient benefits from which immune therapy at a given time point. Results indicate the importance of personalized therapy, specifically the need to identify the type of intervention required by each individual patient at a given point in the disease process. To address this issue will require using biomarkers to stratify patients based on their individual immune status. This article reviews recent and ongoing clinical investigations using immunostimulatory or immunosuppressive therapies against sepsis including non-pharmacological and novel preclinical approaches.

(1) Background: With the rise of multi-/pan-drug resistant (MDR/PDR) pathogens, the less utilized antibiotic Colistin has made a comeback. Colistin fell out of favor due to its small therapeutic range and high potential for toxicity. Today, it is used again as a last resort substance in treating MDR/PDR pathogens. Although new guidelines with detailed recommendations for Colistin dosing are available, finding the right dose in critically ill patients with renal failure remains difficult. Here, we evaluate the efficiency of the current guidelines&rsquo, recommendations by using high resolution therapeutic drug monitoring of Colistin. (2) Methods: We analyzed plasma levels of Colistin and its prodrug colisthimethate sodium (CMS) in 779 samples, drawn from eight PDR-infected ICU patients, using a HPLC-MS/MS approach. The impact of renal function on proper Colistin target levels was assessed. (3) Results: CMS levels did not correlate with Colistin levels. Over-/Underdosing occurred regardless of renal function and mode of renal replacement therapy. Colistin elimination half-time appeared to be longer than previously reported. (4) Conclusion: Following dose recommendations from the most current guidelines does not necessarily lead to adequate Colistin plasma levels. Use of Colistin without therapeutic drug monitoring might be unsafe and guideline adherence does not warrant efficient target levels in critically ill patients.

The current outbreak of coronavirus disease (COVID-19) has reached Germany The majority of people infected present with mild disease, but there are severe cases that need intensive care Unlike other acute infectious diseases progressing to sepsis, the severe courses of COVID19 seemingly show prolonged progression from onset of first symptoms to life-threatening deterioration of (primarily) lung function Diagnosis relies on PCR using specimens from the respiratory tract Severe ARDS reflects the hallmark of a critical course of the disease Preventing nosocomial infections (primarily by correct use of personal protective equipment) and maintenance of hospitals’ operational capability are of utmost importance Departments of Anaesthesia, Intensive Care and emergency medicine will envisage major challenges

Background In Germany, emergency medical teams are staffed with physicians but evidence regarding their prehospital diagnostic accuracy remains poor. Objective To evaluate the out-of-hospital diagnostic accuracy of physician-staffed emergency medical teams (PEMTs). Methods A retrospective observational cohort study involving the Emergency Medical Service Bonn, Germany, from January to December 2004 and 2014 respectively. A total of 8346 patients underwent medical treatment by PEMTs, of which 1960 adult patients (inclusion criteria: ≥18 years of age, hospital diagnosis available) were included for further analysis. Reasons for non-inclusion: death on scene, outpatient, interhospital transfer, mental illness, false alarm, no hospital medical history available. The overall diagnostic accuracy (correct or false) of PEMTs was measured after matching the prehospital diagnosis with the corresponding diagnosis of the hospital. Secondary outcome measures were incidence of common PEMT diagnoses (acute coronary syndrome (ACS), dyspnea, stroke/intracerebral bleeding), recognition rate of a given disease by PEMTs, and prehospital diagnostic accuracy in elderly patients. Results PEMT calls increased 2-fold over a decade (2004: n = 3151 vs. 2014: n = 5195). Overall diagnostic accuracy of PEMTs increased from 87.5% in 2004 to 92.6% in the year 2014. The incidence of common PEMT diagnoses such as ACS, dyspnea or stroke/intracerebral bleeding increased 2-fold from 2004 to 2014. The recognition rate of a given disease by the PEMT varied between 2004 and 2014: an increase was observed when a stroke/intracerebral bleeding was diagnosed (2004: 67% vs. 2014: 83%; p = 0.054), a decreased rate of recognition occurred when a syncope/collapse was diagnosed (2004: 81% vs. 2014: 56%; p = 0.007) and a sepsis appears to be a rare event for EMS personnel (2004: 0% vs. 2014: 23%). Linear regression analysis revealed that the prehospital diagnostic accuracy decreases in the elderly patient. Conclusions The overall prehospital diagnostic accuracy of PEMTs improved between the year 2004 and 2014 respectively. Our findings suggest that the incidence of common diseases (ACS, dyspnea stroke/intracerebral bleeding, sepsis) increased over a 10-year period. Diagnostic accuracy of different diseases varied but generally decreased in the elderly patient. Regular training of EMS personnel and public campaigns should be implemented to improve the diagnostic accuracy in the future. Electronic supplementary material The online version of this article (10.1186/s13049-019-0617-3) contains supplementary material, which is available to authorized users.

In contrast to prehospital emergency medicine, there are no comparable established structures or statutory requirements for structural and procedural organisation, or qualification of personnel and equipment for in-hospital emergency care in Germany. However, in perioperative patients, unexpected complications are fairly common on regular wards. Often, even hours before a possible critical event, warning signs of deterioration are present, which too often go unnoticed. Subsequently, potentially avoidable serious complications or cardiac arrest may occur. The establishment of so-called medical emergency teams (MET) serves to improve the emergency care organisation of the hospital and helps to avoid in-hospital cardiac arrest. The MET is alerted at an early stage of deterioration and uses a preventive therapy approach for pathophysiological deviations of the vital signs. This preventative approach can help to avoid in-hospital cardiac arrest and unplanned admission to an intensive care unit and thus contribute to increase perioperative patient safety.Im Gegensatz zur präklinischen Notfallmedizin existieren in Deutschland bis heute keine vergleichbaren fest etablierten Strukturen oder gesetzliche Vorgaben zur Aufbau- und Ablauforganisation sowie Personalqualifikation und Ausstattung der innerklinischen Notfallversorgung. Bei perioperativen Patienten treten unerwartete Komplikationen auf Normalstation jedoch relativ häufig auf. Oft sind bereits Stunden vor einem möglichen kritischen Ereignis Warnzeichen für eine Verschlechterung zu erkennen, wobei diese zu oft unbemerkt bleiben und es im Verlauf zu vermeidbaren schwerwiegenden Komplikationen oder Herz-Kreislauf-Stillständen kommen kann. Zur Verbesserung der innerklinischen Versorgungsstruktur und zur Vermeidung von innerklinischen Herz-Kreislauf-Stillständen dient die Etablierung sog. medizinischer Einsatzteams (engl. medical emergency teams). Dieser werden im Sinne eines präventiven Therapieansatzes bei erkennbaren Abweichungen der Vitalparameter frühzeitig alarmiert. Durch diesen präventiven Therapieansatz können innerklinische Kreislaufstillstände und ungeplante Aufnahmen auf eine Intensivstation vermieden und die perioperative Patientensicherheit erhöht werden.

Patient outcome after out of hospital cardiac arrest (OHCA) depends on the cardiopulmonary resuscitation (CPR) performance and might also be influenced by organisation of the emergency medical service (EMS) and implementation of guidelines.To assess the rate of return of spontaneous circulation (ROSC) after cardiac arrest to the predicted rate by the ROSC after cardiac arrest (RACA) score over a 15-year period reflecting three different implemented ALS-guidelines in a physician-staffed EMS.All adult patients with non-traumatic OHCA in the EMS of Bonn from 1996 to 2011 were included. Utstein data from three 5-years time periods (1996-2001, 2001-2006, 2006-2011) representing different ALS-guideline implementations were collected. Group comparisons were made in terms of incidence, epidemiology and short-term outcome of CPR with emphasis on changes over time and factors of importance. In each group observed ROSC rate were compared to the predicted ROSC rates (the RACA score).CPR by the ALS unit was attempted in a total of 1989 patients (735, 666, and 588 patients in the first, second and third period, respectively). Average crude incidence of CPR per 100,000 person-years decreased over time (61.3; 55.5; 49.0/100,000/years) while patients treated were significantly older (65.5 ± 16.5; 67.9 ± 15; 68.9 ± 15.7 (p0.001)). Observed ROSC rates were higher than predicted by the RACA score in all time periods, however, admittance to ICU decreased significantly from 50% in the first five-year period to 38% last five-year period (p0.001). From first to third period the proportion of arrests with first observed rhythm of VT/VF arrests did not change (29% vs. 27%, p=0.323) nor there were changes in bystander CPR rates (17% vs. 17%, p=0.520).In a 15-years period and in the setting of a physician-staffed EMS the ROSC rates remain higher than predicted by the RACA score but the admittance to the ICU after OHCA declined significantly. This finding was accompanied by a decrease in CPR incidence and an increase in age of patients.

Der folgerichtige Ansatz, durch Einfuhrung sog. Rapid-response-Teams (RRT), Critical-care-outreach-Teams (CCOT) oder Medical-emergency-Teams (MET, sog. medizinische Notfallteams) diese Lucke in der Versorgungskette zu schliesen, um bereits bei einer beginnenden Verschlechterung des Patienten schneller eingreifen zu konnen, wurde zunachst v. a. im angloamerikanischen Raum verfolgt. Diese Teams sind zentraler Bestandteil eines Rapid-response-Systems (RRS, System des innerklinischen Notfallmanagements), das darauf abzielt, unerwunschte Ereignisse im Krankenhaus zu verhindern. Als ein unerwunschtes Ereignis bezeichnet man hierbei eine Schadigung des Patienten, die zumindest z. T. die Folge einer verzogerten oder inadaquaten Behandlung ist und fur den Patienten mit dem potenziellen Risiko einer nachweisbaren korperlichen Beeintrachtigung oder sogar des Versterbens einhergeht [17]. Das MET wird bereits bei einer sich abzeichnenden vitalen Gefahrdung des Patienten alarmiert, um noch vor dem Eintreten einer akut kritischen Situation den Patienten adaquat zu versorgen und einer qualitativ hoherwertigen sowie standardisierten Behandlung zuzufuhren. Der Begriff des Rapid-response-Systems gilt dabei generell als zusammenfassender Oberbegriff fur ein innerklinisches Notfallmanagement, das auf Notfallteams mit dem Potenzial zur Identifizierung und Therapie von Patienten mit einer akuten Verschlechterung des Vitalzustands basiert ([18], (Abb. 1). Ein MET stellt also kein klassisches Reanimationsteam dar, sondern erfullt daruber hinaus die Aufgabe eines intensivmedizinischen Kompetenzteams, das dem Behandlungsteam auf der Peripherstation einer Klinik zu Hilfe kommt (Tab. 1). Open image in new window Abb. 1 Darstellung der verschiedenen Organisationsformen eines innerklinischen Notfallmanagements. CPR kardiopulmonale Reanimation Open image in new window

AimSurvival rates after out-of-hospital-cardiac-arrest (OHCA) differ widely between EMS systems. Since hypertonic saline appears to improve long-term outcome after OHCA, some local EMS systems have included it in their treatment protocols for OHCA. Our first aim was to give a quality review of one of these protocols. Our second aim was to assess whether short-term survival improves when hypertonic saline is used in resuscitation after OHCA.MethodsMatched pairs were identified for the independent “return of spontaneous circulation (ROSC) after cardiac arrest” (RACA) score variables and for use of ACD-CPR, adrenaline, and amiodarone from the German Resuscitation Registry (GRR) for January 2000 to March 2011. Patients received either 2mlkg−1 hypertonic saline with hydroxyethyl starch (7.2% NaCl with 6% hydroxyethyl starch 200,000/0.5, HyperHAES® [HHS]) infused intravenously within 10min during CPR according to local treatment protocols or standard of care CPR (NON-HHS). The primary endpoint was admission to hospital rate (with spontaneous circulation); secondary endpoint was ROSC rate in relation to RACA score.Results322 matched pairs were defined for 14 variables. Predicted ROSC-rate using RACA-score was similar in HHS (44.63%) and NON-HHS (43.63%; p=0.440). In contrast, 190 (59.0%) HHS patients achieved ROSC compared with only 136 NON-HHS patients (42.2%; χ2: p

Der innerklinische Notfall stellt eine zunehmende Herausforderung fur das Risikomanagement eines Krankenhauses dar und bislang gibt es in Deutschland keine allgemein verbindlichen Empfehlungen fur ein innerklinisches Notfallmanagement. Die Zeitverzogerung bei der Erkennung und Behandlung des kritisch Kranken auf den Bettenstationen fuhrt haufig zu schwerwiegenden Zwischenfallen. Das Konzept der traditionellen Reanimationsteams greift regelhaft zu kurz, da sie erst nach Eintritt einer akuten Verschlechterung bzw. des Herz-Kreislauf-Stillstands aktiviert werden. Die Einfuhrung eines Rapid-response-Systems mit praventivem Ansatz basierend auf einem medizinischen Notallteam (MET) stellt eine unverzichtbare Verbesserung des innerklinischen Notfallmanagements dar. Dafur genugt nicht allein die Umbenennung und Umstrukturierung des bisherigen Reanimationsteams zu einem MET. Vielmehr bedarf es der Einfuhrung standardisierter praventiver Alarmierungskriterien und strukturierter Ablaufe, einer Standardisierung der Ausbildung und der Notfallausrustung in der Klinik sowie der Bereitstellung eines an die Intensivstation angebundenen MET. Fur ein Krankenhaus mit bisher etabliertem Reanimationsteam bedeutet dies einen grundlegenden Paradigmenwechsel mit einem nachhaltigen, interdisziplinaren und institutionalisierten Prozess des Umdenkens und Reorganisierens. Ein klares Bekenntnis und andauernde gemeinsame Anstrengungen des Krankenhaustragers und aller Klinikmitarbeiter ist hierfur Voraussetzung.

Hintergrund Entscheidend fur das Outcome nach plotzlichem Herztod ist die Qualitat der Reanimation (CPR), v. a. der Thoraxkompression. Insbesondere bei CPR unter schwierigen Bedingungen haben mechanische Reanimationssysteme (MRD) mittlerweile eine weite Verbreitung gefunden. Schwerwiegende Verletzungen durch die Anwendung sind hierbei selten und in der Literatur ahnlich haufig wie bei manueller Thoraxkompression beschrieben. Dennoch konnen solche Verletzungen besonders im Postreanimationssetting bedrohlich werden und moglicherweise dem jeweils spezifischen Funktionsprinzip der MRD zugeordnet werden.

The currently valid guidelines for resuscitation of the European Resuscitation Council (ERC) do not give any unambiguous recommendations for "transport with ongoing cardiopulmonary resuscitation". Furthermore, up to now there are no generally accepted criteria for terminating cardiopulmonary resuscitation, apart from certain signs of death. In spite of the generally poor outcome of patients being transported with ongoing cardiopulmonary resuscitation, there are a number of positive case reports and undisputable indications (e.g., in cases with a potentially reversible cause of cardiac arrest). The increase observed over the past few years in the number of patients being transported under cardiopulmonary resuscitation has as yet not been reflected in an improved prognosis for these patients. The use of mechanical chest compression devices with a better quality of chest compression, also under transport conditions, may have an influence on the number transports but this has not yet been evaluated sufficiently with regard to patient outcome. However, the decision to transport a patient resides with the responsible emergency physician who has to evaluate the prognosis for the patient on an individual basis.

Das Uberleben nach einem Herz-Kreislauf-Stillstand bleibt trotz erheblicher Bemuhungen zur Verbesserung der kardiopulmonalen Reanimation (CPR) gering. Die jungsten Anderungen der Internationalen Reanimationsrichtlinien 2005 betonen die Vermeidung von Unterbrechungen der Thoraxkompressionen. So wurden in der Vergangenheit auch verschiedene Reanimationsassistenzgerate mit dem Ziel entwickelt, effektive und kontinuierliche Thoraxkompressionen zu erreichen. Eine dieser Entwicklungen stellt das AutoPulse-System dar. Ausgehend von dem Fallbeispiel eines 66-jahrigen Patienten wird uber den mehr als 3-jahrigen Routineeinsatz des AutoPulse-Systems im Rettungsdienst der Stadt Bonn berichtet. Der AutoPulse stellt dieser Erfahrung nach eine sinnvolle Erweiterung und Bereicherung im Rahmen der Effektivitatsverbesserung der CPR dar.

The oxidoreductase Macrophage Migration Inhibitory Factor (MIF) is discussed as a promising target for immunomodulatory therapy in patients with severe sepsis. Moreover, MIF expresses tautomerase as well as thiol-protein oxidoreductase activities and has a potential role in cellular redox homeostasis, apoptosis inhibition, endotoxin responsiveness as well as regulation of nuclear transcription factors. To further elucidate a potential role of intracellular MIF in severe sepsis, we assessed alterations of intracellular MIF content in peripheral blood leukocytes of patients with severe sepsis in comparison to healthy controls and non-septic patients after major surgery. Intracellular MIF was significantly elevated simultaneously in lymphocytes, B-cells, macrophages and granulocytes of patients with severe sepsis when compared to healthy control individuals (p0.05) and increased when compared to non-septic patients after major surgery. In parallel, plasma MIF levels were elevated in severe sepsis (p0.05). There was no difference of intracellular MIF in lymphocytes, B-cells, macrophages or granulocytes between surviving and non-surviving patients with severe sepsis (p0.05). However, in survivors LPS ex vivo stimulation increased MIF secretion but not in non-survivors of sepsis (p0.05). This finding underlines the role of intracellular MIF in inflammatory diseases. It suggests monitoring of intracellular MIF in further clinical and non-clinical research valuable.

During sepsis, a severe systemic disorder, micronutrients often are decreased. Apoptosis is regarded as an important mechanism in the development of often significant immunosuppression in the course of the disease. This study aimed to investigate alpha-tocopherol and selenium in reference to apoptosis in patients with sepsis. 16 patients were enrolled as soon as they fulfilled the criteria of severe sepsis. 10 intensive care patients without sepsis and 11 healthy volunteers served as controls. alpha-Tocopherol, selenium and nucleosomes were measured in serum. Phosphatidylserine externalization and Bcl-2 expression were analyzed in T-cells by flow cytometry. Serum alpha-tocopherol and selenium were decreased in severe sepsis but not in non-septic critically ill patients (p < 0.05). Conversely, markers of apoptosis were increased in sepsis but not in critically ill control patients: Nucleosomes were found to be elevated 3 fold in serum (p < 0.05) and phosphatidylserine was externalized on an expanded subpopulation of T-cells (p < 0.05) while Bcl-2 was expressed at lower levels (p < 0.05). The decrease of micronutrients correlated with markers of accelerated apoptosis. Accelerated apoptosis in sepsis is associated with low alpha-tocopherol and selenium. The results support the investigation of micronutrient supplementation strategies in severe sepsis.

An experimental method is demonstrated that allows determination of the ratio between the electric ($E1$) and magnetic ($M1$) transition dipole moments in the $A\ensuremath{-}X$ band of OH, including their relative sign. Although the transition strengths differ by more than 3 orders of magnitude, the measured $M1$-to-$E1$ ratio agrees with the ratio of the ab initio calculated values to within 3%. The relative sign is found to be negative, also in agreement with theory.

We present an experimental and theoretical investigation of rotationally inelastic transitions of OH, prepared in the X(2)Π, v = 0, j = 3/2 F1f level, in collisions with molecular hydrogen (H2 and D2). In a crossed beam experiment, the OH radicals were state selected and velocity tuned over the collision energy range 75-155 cm(-1) using a Stark decelerator. Relative parity-resolved state-to-state integral cross sections were determined for collisions with normal and para converted H2. These cross sections, as well as previous OH-H2 measurements at 595 cm(-1) collision energy by Schreel and ter Meulen [J. Chem. Phys. 105, 4522 (1996)], and OH-D2 measurements for collision energies 100-500 cm(-1) by Kirste et al. [Phys. Rev. A 82, 042717 (2010)], were compared with the results of quantum scattering calculations using recently determined ab initio potential energy surfaces [Ma et al., J. Chem. Phys. 141, 174309 (2014)]. Good agreement between the experimental and computed relative cross sections was found, although some structure seen in the OH(j = 3/2 F1f → j = 5/2 F1e) + H2(j = 0) cross section is not understood.

Objective: Cardiac surgery causes induction and release of inflammatory mediators that may be regulated by genetic background. Macrophage migration inhibitory factor (MIF) is a proinflammatory mediator that is known to be up-regulated in patients undergoing cardiac operations. Here we analyzed genotype distribution and allele frequency of the MIF-173*G/C single nucleotide polymorphism (SNP) and MIF plasma levels in patients undergoing surgical revascularization with (on-pump, n = 45) and without (off-pump, n = 34) cardiopulmonary bypass (CPB). Methods: Genotyping was performed using a real-time PCR-based system with a hybridization probe system specific for the MIF-173*G/C SNP. In on-pump patients, blood samples were drawn before start of CPB, after termination of CPB and 12 h postoperatively. In off-pump patients, blood samples were collected before stabilizer placement, after removal of the stabilizer and 12 h postoperatively. MIF levels were measured using ELISA technique. Results: Genotype distribution and allele frequencies were comparable between on-pump and off-pump patients. When comparing patients according to MIF genotype, a significant increase of MIF plasma levels after completed coronary bypass grafting using CPB was found in patients heterozygous for the MIF-173*G/C SNP (p < 0.05). Moreover, on-pump patients showed significantly decreased MIF plasma levels after 12 h postoperatively (p < 0.05). In off-pump patients, MIF plasma levels were not significantly different over the time-course and were independent of the genotype. Conclusions: Patients carrying the C-allele showed significantly increased levels of the proinflammatory cytokine MIF compared to G/G homozygous when revascularization was carried out using CPB. The G/C genotype may be associated with a severe inflammatory reaction and therefore preoperative screening could be beneficial for patients undergoing cardiac surgery using CPB.

In emergency medicine accidental hypothermia (

The oxidoreductase MIF is currently discussed as a new promising target of immunomodulatory therapy in patients with severe sepsis. An increasing body of evidence attributes an important role especially to intracellular MIF for regulation of endotoxin responsiveness as well as regulation of nuclear transcription factors. Up to now, measurement of MIF relied on ELISA techniques, lacking the ability to directly measure intracellular MIF and distinguish between different leukocyte subpopulations. Therefore, we developed a sensitive and robust flow cytometry-based method to reliably detect intracellular levels of MIF. This method can readily be applied in cultured cells as well as in subsets of human leukocytes in whole blood. Intracellular MIF content of whole-blood leukocyte subsets is detected simultaneously, and is individually determined for T-lymphocytes, B-lymphocytes, macrophages, and granulocytes, respectively. When tested in an ex vivo whole-blood stimulation system using PMA/Ionomycin the intracellular MIF content doubled in CD3+ T-lymphocytes and increased threefold in CD14+ macrophages. Baseline intracellular MIF levels of different leukocyte subpopulations were quantified in 22 healthy blood donors. Baseline intracellular MIF levels in T-lymphocytes are twice as high compared to those in B-lymphocytes and macrophages.

Urosepsis is defined as sepsis caused by urinary tract infection. This occurs in 25% of all sepsis cases. Because of the increasing incidence of sepsis, this entity will be seen more frequently in medical practice and outpatient units. The immediate identification and treatment of the septic focus is crucial. Depending on severity, early reconstitution of adequate oxygen delivery has parallel priority, therefore necessitating intensive care unit treatment within the first hours. Therapy should consist of eliminating the infectious focus, antimicrobial treatment, supportive therapy, and special sepsis therapy.

Die Sepsis gehort nach wie vor zu den haufigsten Todesursachen bei Intensivpatienten. Der Pathogenese der Erkrankung liegt ein komplexes Immungeschehen zugrunde. Neueste Erkenntnisse zeigen, dass Zellen des Abwehrsystems bei der Sepsis im Rahmen der Immunantwort haufig eine Signalkaskade aktivieren, die zum programmierten Zelltod, der sog. Apoptose, fuhrt. Apoptose von Leukozyten wurde sowohl im Tiermodell als auch bei Patienten mit Sepsis beobachtet. Bei der Regulation der Apoptose spielen das mitochondriale Protein Bcl-2 und die zytoplasmatische Enzymkaskade der Kaspasen eine wesentliche Rolle. Durch Uberexprimierung von Bcl-2 oder Hemmung der Kaspasen konnte im Tiermodell der Sepsis ein deutlicher Uberlebensvorteil demonstriert werden. Erste Arbeiten zeigten auch die Relevanz der Apoptose bei Patienten mit schwerer Sepsis. Ziel aktueller Forschung auf diesem Gebiet ist es, durch gezielte Beeinflussung der Apoptose neue molekulare Ansatze zur Therapie der Sepsis zu finden.

Background Heparin-induced thrombocytopenia (HIT) causes thromboembolic complications which threaten life and limb. Heparin is administered to virtually every critically ill patient as a protective measure against thromboembolism. Argatroban is a promising alternative anticoagulant agent. However, a safe dose which still provides effective thromboembolic prophylaxis without major bleeding still needs to be identified. Methods Critically ill patients (n = 42) diagnosed with HIT at a tertiary medical center intensive care unit from 2005 to 2010 were included in this retrospective analysis. Patient records were perused for preexisting history of HIT, heparin dosage before HIT, argatroban dosage, number of transfusions required, thromboembolic complications and length of ICU stay (ICU LOS). Patients were allocated to Simplified Acute Physiology Scores above and below 30 (SAPS >30, SAPS 0.05) to achieve effective anticoagulation. No thromboembolic complications were encountered. Argatroban had to be discontinued temporarily in 16 patients for a total of 57 times due to diagnostic or surgical procedures, supratherapeutic aPTT and bleeding without increasing the number of transfusions. A history of HIT was associated with a shorter ICU LOS and significantly reduced transfusion need when compared to patients with no history of HIT. Cost calculation favour argatroban due to increased transfusion needs during heparin administration and increase ICU LOS. Conclusion Argatroban can be used at doses

A considerable potential for neurogenesis has been identified in the epileptic rat hippocampus. Here, we explore this feature in human patients suffering from chronic mesial temporal lobe epilepsy. Immunohistochemical detection of the neurodevelopmental antigen nestin was used to detect neural precursor cells, and cell-type specific markers were employed to study their histogenetic origin and potential for neuronal or glial differentiation. The ontogenetic regulation of nestin-positive precursors was established in human control brains (week 19 of gestation–15 years of age). A striking increase of nestin-immunoreactive cells within the hilus and dentate gyrus could be observed in a group of young patients with temporal lobe epilepsy (TLE) and surgical treatment before age 2 years compared to adult TLE patients and controls. The cellular morphology and regional distribution closely resembled nestin-immunoreactive granule-cell progenitors transiently expressed during prenatal human hippocampus development. An increased Ki-67 proliferation index and clusters of supragranular nestin-immunoreactive cells within the molecular layer of the dentate gyrus were also noted in the group of young TLE patients. Confocal studies revealed colocalization of nestin and the βIII isoform of tubulin, indicating a neuronal fate for some of these cells. Vimentin was consistently expressed in nestin-immunoreactive cells, whereas cell lineage-specific markers, i.e., glial fibrillary acidic protein, MAP2, neurofilament protein, NeuN, or calbindin D-28k failed to colocalize. These findings provide evidence for increased neurogenesis in pediatric patients with early onset of temporal lobe epilepsy and/or point towards a delay in hippocampal maturation in a subgroup of patients with TLE. Hippocampus 2001;11:311–321. © 2001 Wiley-Liss, Inc.

Whereas atom-molecule collisions have been studied with complete quantum-state resolution, interactions between two state-selected molecules have proven much harder to probe. Here, we report the measurement of state-resolved inelastic scattering cross sections for collisions between two open-shell molecules that are both prepared in a single quantum state. Stark-decelerated hydroxyl (OH) radicals were scattered with hexapole-focused nitric oxide (NO) radicals in a crossed-beam configuration. Rotationally and spin-orbit inelastic scattering cross sections were measured on an absolute scale for collision energies between 70 and 300 cm(-1). These cross sections show fair agreement with quantum coupled-channels calculations using a set of coupled model potential energy surfaces based on ab initio calculations for the long-range nonadiabatic interactions and a simplistic short-range interaction. This comparison reveals the crucial role of electrostatic forces in complex molecular collision processes.

The currently valid guidelines for resuscitation of the European Resuscitation Council (ERC) do not give any unambiguous recommendations for "transport with ongoing cardiopulmonary resuscitation". Furthermore, up to now there are no generally accepted criteria for terminating cardiopulmonary resuscitation, apart from certain signs of death. In spite of the generally poor outcome of patients being transported with ongoing cardiopulmonary resuscitation, there are a number of positive case reports and undisputable indications (e.g., in cases with a potentially reversible cause of cardiac arrest). The increase observed over the past few years in the number of patients being transported under cardiopulmonary resuscitation has as yet not been reflected in an improved prognosis for these patients. The use of mechanical chest compression devices with a better quality of chest compression, also under transport conditions, may have an influence on the number transports but this has not yet been evaluated sufficiently with regard to patient outcome. However, the decision to transport a patient resides with the responsible emergency physician who has to evaluate the prognosis for the patient on an individual basis.

Introduction Sudden cardiac arrest is one of the most frequent causes of death in the world. In highly qualified emergency medical service (EMS) systems, including well-trained emergency physicians, spontaneous circulation may be restored in up to 53% of patients at least until admission to hospital. Compared with these highly qualified EMS systems, markedly lower success rates are observed in other systems. These data clearly show that there are considerable differences between EMS systems concerning treatment success following cardiac arrest and resuscitation, although in all systems international guidelines for resuscitation are used. In this study, we investigated the impact of response time reliability (RTR) on cardiopulmonary resuscitation (CPR) incidence and resuscitation success by using the return of spontaneous circulation (ROSC) after cardiac arrest (RACA) scores and data from seven German EMS systems participating in the German Resuscitation Registry. Methods Anonymised patient data after out-of-hospital cardiac arrest gathered from seven EMS systems in Germany from 2006 to 2009 were analysed with regard to socioeconomic factors (population, area and EMS unit-hours), process quality (RTR, CPR incidence, special CPR measures and prehospital cooling), patient factors (age, gender, cause of cardiac arrest and bystander CPR). End points were defined as ROSC, admission to hospital, 24-hour survival and hospital discharge rate. χ2 tests, odds ratios and the Bonferroni correction were used for statistical analyses. Results Our present study comprised 2,330 prehospital CPR patients at seven centres. The incidence of sudden cardiac arrest ranged from 36.0 to 65.1/100,000 inhabitants/year. We identified two EMS systems (RTR < 70%) that reached patients within 8 minutes of the call to the dispatch centre 62.0% and 65.6% of the time, respectively. The other five EMS systems (RTR > 70%) reached patients within 8 minutes of the call to the dispatch centre 70.4% up to 95.5% of the time. EMS systems arriving relatively later at the patients side (RTR < 70%) initiate CPR less frequently and admit fewer patients alive to hospital (calculated per 100,000 inhabitants/year) (CPR incidence (1/100,000 inhabitants/year) RTR > 70% = 57.2 vs RTR < 70% = 36.1, OR = 1.586 (99% CI = 1.383 to 1.819); P < 0.01) (admitted to hospital with ROSC (1/100,000 inhabitants/year) RTR > 70% = 24.4 vs RTR < 70% = 15.6, OR = 1.57 (99% CI = 1.274 to 1.935); P < 0.01). Using ROSC rate and the multivariate RACA score to predict outcomes, we found that the two groups did not differ, but ROSC rates were higher than predicted in both groups (ROSC RTR > 70% = 46.6% vs RTR < 70% = 47.3%, OR = 0.971 (95% CI = 0.787 to 1.196); P = n.s.) (ROSC RACA RTR > 70% = 42.4% vs RTR < 70% = 39.5%, OR = 1.127 (95% CI = 0.911 to 1.395); P = n.s.) Conclusion This study demonstrates that, on the level of EMS systems, faster ones more often initiate CPR and increase the number of patients admitted to hospital alive. Furthermore, we show that, with very different approaches, all centres that adhere to and are intensely trained according to the 2005 European Resuscitation Council guidelines are superior and, on the basis of international comparisons, achieve excellent success rates following CPR. peerReviewed

We here report coherent reflection of thermal He atom beams from various microscopically rough surfaces at grazing incidence. For a sufficiently small normal component $k_z$ of the incident wave-vector of the atom the reflection probability is found to be a function of $k_z$ only. This behavior is explained by quantum-reflection at the attractive branch of the Casimir-van der Waals interaction potential. For larger values of $k_z$ the overall reflection probability decreases rapidly and is found to also depend on the parallel component $k_x$ of the wave-vector. The material specific $k_x$ dependence for this classical reflection at the repulsive branch of the potential is explained qualitatively in terms of the averaging-out of the surface roughness under grazing incidence conditions., 4 pages, 4 figures

Background Macrophage migration inhibitory factor (MIF) plays an important regulatory role in sepsis. In the promoter region a C/G single nucleotide polymorphism (SNP) at position -173 (rs755622) and a CATT5-8 microsatellite at position -794 are related to modified promoter activity. The purpose of the study was to analyze their association with the incidence and outcome of severe sepsis. Methods Genotype distributions and allele frequencies in 169 patients with severe sepsis, 94 healthy blood donors and 183 postoperative patients without signs of infection or inflammation were analyzed by real time PCR and Sequence analysis. All included individuals were Caucasians. Results Genotype distribution and allele frequencies of severe sepsis patients were comparable to both control groups. However, the genotype and allele frequencies of both polymorphisms were associated significantly with the outcome of severe sepsis. The highest risk of dying from severe sepsis was detectable in patients carrying a haplotype with the alleles -173 C and CATT7 (p = 0.0005, fisher exact test, RR = 1,806, CI: 1.337 to 2.439). Conclusion The haplotype with the combination of the -173 C allele and the -794 CATT7 allele may not serve as a marker for susceptibility to sepsis, but may help identify septic patients at risk of dying.

Regional anaesthesia is commonly used for elective caesarean section. The aim of this study was to investigate whether there is a positive effect of either spinal or epidural anaesthesia on postoperative analgesic requirements and pain relief.The analgesic effect of either spinal or epidural induction of perispinal anaesthesia have been compared in 132 women (ASA I or II) scheduled for elective caesarean section, all having epidural catheterization for perioperative anaesthesia and postoperative analgesia. The patients were randomized into two groups. To achieve a sensory block height to the level of the sixth thoracic dermatome, the parturients received isobaric bupivacaine 0.5% and 5 microg sufentanil intrathecally or ropivacaine 0.75% and 10 microg sufentanil epidurally. For postoperative analgesia, all patients used patient-controlled epidural analgesia at identical settings [bolus of ropivacaine 0.133% (11-15 mg according to patient's height), lock-out time 1 h]. Intraoperative and postoperative pain was recorded using a visual analogue pain score as well as analgesic requirements over the first 24 h after surgery.One hundred and twenty-five patients completed the study. There were no differences in patient-controlled epidural analgesic requirements between groups. During surgery, the pain score on a visual analogue scale was more intense with epidural anaesthesia than with spinal anaesthesia (P0.05). For the whole 24 h observation period, the area under the curve for pain was lower with spinal anaesthesia (P0.0005). At almost all postoperative time points, visual analogue scale scores at rest and during mobilization were lower with spinal anaesthesia (P0.05), which was accompanied by less motor blockade and lower frequency of adverse effects. More patients with epidural anaesthesia received supplemental analgesic medication.In parturients undergoing elective caesarean section, postoperative use of epidural ropivacaine via patient-controlled epidural analgesia is similar after spinal and epidural anaesthesia. Spinal anaesthesia is, however, accompanied with less postoperative pain, use of additional analgesics and side-effects.

During therapeutic hyperbaric oxygenation lymphocytes are exposed to high partial pressures of oxygen. This study aimed to analyze the mechanism of apoptosis induction by hyperbaric oxygen. For intervals of 0.5-4 h Jurkat-T-cells were exposed to ambient air or oxygen atmospheres at 1-3 absolute atmospheres. Apoptosis was analyzed by phosphatidylserine externalization, caspase-3 activation and DNA-fragmentation using flow cytometry. Apoptosis was already induced after 30 min of hyperbaric oxygenation (HBO, P < 0.05). The death receptor Fas was downregulated. Inhibition of caspase-9 but not caspase-8 blocked apoptosis induction by HBO. Hyperbaric oxygen caused a loss of mitochondrial membrane potential and caspase-9 induction. The mitochondrial pro-survival protein Bcl-2 was upregulated, and antagonizing Bcl-2 function potentiated apoptosis induction by HBO. In conclusion, a single exposure to hyperbaric oxygenation induces lymphocyte apoptosis by a mitochondrial and not a Fas-related mechanism. Regulation of Fas and Bcl-2 may be regarded as protective measures of the cell in response to hyperbaric oxygen.

3D holographic gratings with variable periodicity represent a central part of an optical sensing system. Periodic spatial modulation of the refractive index in all three dimensions is holographically induced by multiple beam interference. The periodicity of the resulting volume diffractive optical structure is controlled by the recording beam geometry. The recording medium is a photosensitive polymer. An experimental setup for creating and analyzing such 3D gratings is presented as well as first results achieved in a 300 μm thick photopolymer sample.