[Evaluation of the project for the introduction of bystander resuscitation in schools in North Rhine-Westphalia]. / Evaluation des Projekts zur Einführung von Laienreanimation an Schulen in Nordrhein-Westfalen.

BACKGROUND: Teaching of resuscitation measures is not mandatory in all schools in Germany. It is currently limited to individual, partly mandatory projects despite a low bystander resuscitation rate. For this reason, the Ministry for Schools and Education of North Rhine-Westphalia initiated the project "Bystander resuscitation at schools in NRW" in March 2017. OBJECTIVE: The aim of this work was to evaluate this project. MATERIAL AND METHODS: All secondary schools in North Rhine-Westphalia were invited to participate in the project. Medical partners from each administrative district took part, who carried out resuscitation training with existing concepts for teacher or student training. After a 3-year period, the evaluation was carried out using standardized questionnaires for school headmasters, teachers and students. RESULTS: In total, more than 40,000 pupils from 249 schools in NRW could be trained in resuscitation within the project with 6 different concepts. Of the students 85% answered the questions regarding resuscitation correctly and overall felt safe in resuscitation measures. The one-off investment requirement for all schools is roughly 4-6.5 million € and around 340,000 € in each budget year. CONCLUSION: A legal constitution and funding are necessary for a nationwide introduction of resuscitation in schools. All established concepts are effective, therefore each school can use them exactly according to their needs, optimally in a stepped form. Training for teachers should focus on resuscitation.

Resuscitation with Hydroxyethyl Starch Maintains Hemodynamic Coherence in Ovine Hemorrhagic Shock.

BACKGROUND: Fluid resuscitation in hemorrhagic shock aims to restore hemodynamics and repair altered microcirculation. Hemodynamic coherence is the concordant performance of macro- and microcirculation. The present study on fluid therapy in hemorrhagic shock hypothesized that the choice of fluid (0.9% sodium chloride [saline group] or balanced 6% hydroxyethyl starch 130/0.4 [hydroxyethyl starch group]) impacts on hemodynamic coherence. METHODS: After instrumentation, 10 sheep were bled up to 30 ml/kg body weight of blood stopping at a mean arterial pressure of 30 mmHg to establish hemorrhagic shock. To reestablish baseline mean arterial pressure, they received either saline or hydroxyethyl starch (each n = 5). Hemodynamic coherence was assessed by comparison of changes in mean arterial pressure and both perfused vessel density and microvascular flow index. RESULTS: Bleeding of 23 ml/kg blood [21; 30] (median [25th; 75th percentile]) in the saline group and 24 ml/kg [22; 25] (P = 0.916) in the hydroxyethyl starch group led to hemorrhagic shock. Fluid resuscitation reestablished baseline mean arterial pressure in all sheep of the hydroxyethyl starch group and in one sheep of the saline group. In the saline group 4,980 ml [3,312; 5,700] and in the hydroxyethyl starch group 610 ml [489; 615] of fluid were needed (P = 0.009). In hemorrhagic shock perfused vessel density (saline from 100% to 83% [49; 86]; hydroxyethyl starch from 100% to 74% [61; 80]) and microvascular flow index (saline from 3.1 [2.5; 3.3] to 2.0 [1.6; 2.3]; hydroxyethyl starch from 2.9 [2.9; 3.1] to 2.5 [2.3; 2.7]) decreased in both groups. After resuscitation both variables improved in the hydroxyethyl starch group (perfused vessel density: 125% [120; 147]; microvascular flow index: 3.4 [3.2; 3.5]), whereas in the saline group perfused vessel density further decreased (64% [62; 79]) and microvascular flow index increased less than in the hydroxyethyl starch group (2.7 [2.4; 2.8]; both P < 0.001 for saline vs. hydroxyethyl starch). CONCLUSIONS: Resuscitation with hydroxyethyl starch maintained coherence in hemorrhagic shock. In contrast, saline only improved macro- but not microcirculation. Hemodynamic coherence might be influenced by the choice of resuscitation fluid.

A Prospective Observational Study of Rational Fluid Therapy in Asian Intensive Care Units: Another Puzzle Piece in Fluid Therapy.

INTRODUCTION: Fluid therapy in critically ill patients, especially timing and fluid choice, is controversial. Previous randomized trials produced conflicting results. This observational study evaluated the effect of colloid use on 90-day mortality and acute kidney injury (RIFLE F) within the Rational Fluid Therapy in Asia (RaFTA) registry in intensive care units. MATERIALS AND METHODS: RaFTA is a prospective, observational study in Asian intensive care unit (ICU) patients focusing on fluid therapy and related outcomes. Logistic regression was performed to identify risk factors for increased 90-day mortality and acute kidney injury (AKI). RESULTS: Twenty-four study centers joined the RaFTA registry and collected 3,187 patient data sets from November 2011 to September 2012. A follow-up was done 90 days after ICU admission. For 90-day mortality, significant risk factors in the overall population were sepsis at admission (OR 2.185 [1.799; 2.654], p < 0.001), cumulative fluid balance (OR 1.032 [1.018; 1.047], p < 0.001), and the use of vasopressors (OR 3.409 [2.694; 4.312], p < 0.001). The use of colloids was associated with a reduced risk of 90-day mortality (OR 0.655 [0.478; 0.900], p = 0.009). The initial colloid dose was not associated with an increased risk for AKI (OR 1.094 [0.754; 1.588], p = 0.635). CONCLUSION: RaFTA adds the important finding that colloid use was not associated with increased 90-day mortality or AKI after adjustment for baseline patient condition. CLINICAL SIGNIFICANCE: Early resuscitation with colloids showed potential mortality benefit in the present analysis. Elucidating these findings may be an approach for future research. HOW TO CITE THIS ARTICLE: Jacob M, Sahu S, Singh YP, Mehta Y, Yang K-Y, Kuo S-W, et al. A Prospective Observational Study of Rational Fluid Therapy in Asian Intensive Care Units: Another Puzzle Piece in Fluid Therapy. Indian J Crit Care Med 2020;24(11):1028-1036.

Combination of problem-based learning with high-fidelity simulation in CPR training improves short and long-term CPR skills: a randomised single blinded trial.

BACKGROUND: Performance of sufficient cardiopulmonary resuscitation (CPR) by medical personnel is critical to improve outcomes during cardiac arrest. It has however been shown that even health care professionals possess a lack of knowledge and skills in CPR performance. The optimal method for teaching CPR remains unclear, and data that compares traditional CPR instructional methods with newer modalities of CPR instruction are needed. We therefore conducted a single blinded, randomised study involving medical students in order to evaluate the short- and long-term effects of a classical CPR education compared with a bilateral approach to CPR training, consisting of problem-based learning (PBL) plus high fidelity simulation. METHODS: One hundred twelve medical students were randomized during a curricular anaesthesiology course to a control (n = 54) and an intervention (n = 58) group. All participants were blinded to group assignment and partook in a 30-min-lecture on CPR basics. Subsequently, the control group participated in a 90-min tutor-guided CPR hands-on-training. The intervention group took part in a 45-min theoretical PBL module followed by 45 min of high fidelity simulated CPR training. The rate of participants recognizing clinical cardiac arrest followed by sufficiently performed CPR was the primary outcome parameter of this study. CPR performance was evaluated after the intervention. In addition, a follow-up evaluation was conducted after 6 months. RESULTS: 51.9% of the intervention group met the criteria of sufficiently performed CPR as compared to only 12.5% in the control group on the day of the intervention (p = 0.007). Hands-off-time as a marker for CPR continuity was significantly less in the intervention group (24.0%) as compared to the control group (28.3%, p = 0.007, Hedges' g = 1.55). At the six-month follow-up, hands-off-time was still significantly lower in the intervention group (23.7% vs. control group: 31.0%, p = 0.006, Hedges' g = 1.88) but no significant difference in sufficiently performed CPR was detected (intervention group: 71.4% vs. control group: 54.5%, p = 0.55). CONCLUSION: PBL combined with high fidelity simulation training leads to a measurable short-term increase in initiating sufficient CPR by medical students immediately after training as compared to classical education. At six month post instruction, these differences remained only partially.

6% Hydroxyethyl starch (HES 130/0.4) diminishes glycocalyx degradation and decreases vascular permeability during systemic and pulmonary inflammation in mice.

BACKGROUND: Increased vascular permeability is a pathophysiological hallmark of sepsis and results in increased transcapillary leakage of plasma fluid, hypovolemia, and interstitial edema formation. 6% hydroxyethyl starch (HES 130/0.4) is commonly used to treat hypovolemia to maintain adequate organ perfusion and oxygen delivery. The present study was designed to investigate the effects of 6% HES 130/0.4 on glycocalyx integrity and vascular permeability in lipopolysaccharide (LPS)-induced pulmonary inflammation and systemic inflammation in mice. METHODS: 6% HES 130/0.4 or a balanced electrolyte solution (20 ml/kg) was administered intravenously 1 h after cecal ligation and puncture (CLP) or LPS inhalation. Sham-treated animals receiving 6% HES 130/0.4 or the electrolyte solution served as controls. The thickness of the endovascular glycocalyx was visualized by intravital microscopy in lung (LPS inhalation model) or cremaster muscle (CLP model). Syndecan-1, hyaluronic acid, and heparanase levels were measured in blood samples. Vascular permeability in the lungs, liver, kidney, and brain was measured by Evans blue extravasation. RESULTS: Both CLP induction and LPS inhalation resulted in increased vascular permeability in the lung, liver, kidney, and brain. 6% HES 130/0.4 infusion led to significantly reduced plasma levels of syndecan-1, heparanase, and hyaluronic acid, which was accompanied by a preservation of the glycocalyx thickness in postcapillary venules of the cremaster (0.78 ± 0.09 µm vs. 1.39 ± 0.10 µm) and lung capillaries (0.81 ± 0.09 µm vs. 1.49 ± 0.12 µm). CONCLUSIONS: These data suggest that 6% HES 130/0.4 exerts protective effects on glycocalyx integrity and attenuates the increase of vascular permeability during systemic inflammation.

Preoperative anemia and extensive transfusion during stay-in-hospital are critical for patient`s mortality: A retrospective multicenter cohort study of oncological patients undergoing radical cystectomy.

BACKGROUND: Preoperative anemia and allogeneic blood transfusions (ABTs) may affect outcomes in cancer surgery. The prevalence of anemia, the use of ABTs, the risks of transfusions, lengths of stay and mortality of oncological patients undergoing radical cystectomy were investigated in three University Hospitals in Germany. PATIENTS AND METHODS: Hospital records of 220 consecutive patients undergoing radical cystectomy from 2010 to 2012 were retrospectively analyzed for independent risk factors of ABT and unfavorable outcomes (readmission, increased length of stay (LOS) or death) using multivariate regression analysis. RESULTS: Preoperative anemia was present in 40%. 70% of patients received blood transfusions. Low preoperative and intraoperative nadir hemoglobin levels were associated with receipt of ABT (OR 1.33, P = 0.04 and OR 2.94, P < 0.001 respectively). Transfusion of ten or more red blood cell units (RBCs) during the entire hospital stay was a predictor of an increased LOS (P < 0.001) and death (OR 52, 95%CI [5.9, 461.3], P < 0.001), compared to non-transfused patients. Preoperative ABT and ASA scores were associated with ≥10RBCs. CONCLUSION: Anemic patients undergoing radical cystectomy had a high risk to receive ABTs. Preoperative transfusions and transfusion of ≥10RBCs during the entire hospital stay may increase patient`s mortality. Prospective, randomized controlled studies have to follow this study.

Treating Anemia in the Preanesthesia Assessment Clinic: Results of a Retrospective Evaluation.

BACKGROUND: Perioperative anemia is challenging during hospital stay because anemia and red blood cell (RBC) transfusions are associated with an increased morbidity and mortality. With the implementation of patient blood management (PBM), a preanesthesia assessment clinic to screen and treat anemia before elective surgery was institutionalized at Muenster University Hospital, Germany. The main objective of this study was to evaluate the association between treating preoperative anemic patients with intravenous iron (IVI) and (primarily) presurgical hemoglobin levels and (secondarily) use of RBCs and mortality. METHODS: Between April 1, 2014, and July 4, 2016, patients scheduled for elective surgery with a risk for RBC transfusions >10% in 2013 were screened for preoperative anemia and, if indicated, treated with IVI. Patients' data, time span between visit in the anesthesia/PBM clinic and surgery, demographic data, type of surgery, the difference of hemoglobin levels between visit and surgery, RBC transfusion, infectious-related International Classification of Disease codes during hospital stay, and 1-year survival were determined retrospectively by screening electronic data files. In addition, patients were interviewed about adverse events, health-related events, and infections via telephone 30, 90, and 365 days after visiting the anesthesia/PBM clinic. RESULTS: A total of 1101 patients were seen in the anesthesia/PBM clinic between days -28 and -1 (median [Q1-Q3], -3 days [-1, -9 days]) before elective surgery. Approximately 29% of patients presented with anemia, 46.8% of these anemic patients were treated with ferric carboxymaltose (500-1000 mg).In the primary analysis, hemoglobin levels at median were associated with a reduction between the visit in the anesthesia/PBM clinic and the surgery in all nonanemic patients on beginning of medical treatment (nonanemic patients at median -2.8 g/dL [-4, -0.9 g/dL], while anemic patients without IVI presented with median differences of -0.8 g/dL [-2, 0 g/dL] and anemic patients with IVI of 0 g/dL [-1.0, 0.5 g/dL]). Hemoglobin levels raised best at substitution 22-28 days before surgery (0.95 g/dL [-0.35, 1.18 g/dL]). Due to the selection criteria, transfusion rates were high in the cohort. Overall, there was no association between IVI treatment and the use of RBC transfusions (odds ratio for use of RBCs in anemic patients, no IVI versus IVI: 1.14; 95% confidence interval, 0.72-1.82). Patients treated with or without IVI presented a comparable range of International Classification of Disease codes related to infections. Telephone interviews indicated similar adverse events, health-related events, and infections. Cox regression analysis showed an association between anemia and reduced survival, regardless of IVI. CONCLUSIONS: An anemia clinic within the preanesthesia assessment clinic is a feasible and effective approach to treat preoperative anemia. The IVI supplementation was safe but was associated with decreased RBC transfusions in gynecology/obstetric patients only. The conclusions from this retrospective analysis have to be tested in prospective, controlled trials.

A better understanding of ambulance personnel's attitude towards real-time resuscitation feedback.

OBJECTIVE: High-quality chest compressions during cardiopulmonary resuscitation (CPR) play a significant role in surviving cardiac arrest. Chest-compression quality can be measured and corrected by real-time CPR feedback devices, which are not yet commonly used. This article looks at the acceptance of such systems in comparison of equipped and unequipped personnel. DESIGN: Two groups of emergency medical services' (EMS) personnel were interviewed using standardized questionnaires. SETTING: The survey was conducted in the German cities Dortmund and Münster. PARTICIPANTS: Overall, 205 persons participated in the survey: 103 paramedics and emergency physicians from the Dortmund fire service and 102 personnel from the Münster service. INTERVENTION: The staff of the Dortmund service were not equipped with real-time feedback systems. The test group of equipped personnel of the ambulance service of Münster Fire brigade uses real-time feedback systems since 2007. MAIN OUTCOME MEASURE: What is the acceptance level of real-time feedback systems? Are there differences between equipped and unequipped personnel? RESULTS: The total sample is receptive towards real-time feedback systems. More than 80% deem the system useful. However, this study revealed concerns and prejudices by unequipped personnel. Negative ratings are significantly lower at the Münster site that is experienced with the use of the real-time feedback system in contrast to the Dortmund site where no such experience exists-the system's use in daily routine results in better evaluation than the expectations of unequipped personnel. CONCLUSIONS: Real-time feedback systems receive overall positive ratings. Prejudices and concerns seem to decrease with continued use of the system.

Post-Operative Iron Carboxymaltose May Have an Effect on Haemoglobin Levels in Cardiothoracic Surgical Patients on the ICU - an Observational Pilot Study about Anaemia Treatment with Intravenous Iron.

BACKGROUND: Post-operative anaemia is associated with increased morbidity and mortality. Positive effects of post-operative intravenous iron (IVI) after elective orthopaedic, abdominal and genitourinary surgery have been reported. The current observational trial investigated the prevalence of post-operative anaemia, the effect of IVI on haemoglobin levels, the use of blood transfusions and diagnoses related to infections. METHODS: 1,265 patients on five ICUs of Münster University Hospital were screened for post-operative anaemia. On one ICU, patients were screened for iron deficiency and, if indicated, supplemented with 500 mg of ferric carboxymaltose. Primary outcome measures were haemoglobin levels, C-reactive protein, white blood cell count, transfusion requirements, documented infection and antibiotic treatment. RESULTS: Anaemia was prevalent in 86.2% of patients upon ICU admission. 429 patients were screened for iron deficiency anaemia. 95 patients were eligible, 35 were treated with IVI. An increase of +0.4 g/dl in Hb levels 7 days after IVI compared to -0.1 g/dl in non-treated anaemic patients was observed. The number of RBC transfusions, ICD codes related to infections and infectious parameters were similar between groups. Conclusions: IVI treatment was safe and resulted in higher median Hb levels. Randomized controlled trials are required to support the hypotheses of this study.

Long-term Effects of Remote Ischemic Preconditioning on Kidney Function in High-risk Cardiac Surgery Patients: Follow-up Results from the RenalRIP Trial.

BACKGROUND: In a multicenter, randomized trial, the authors enrolled patients at high-risk for acute kidney injury as identified by a Cleveland Clinic Foundation score of 6 or more. The authors enrolled 240 patients at four hospitals and randomized them to remote ischemic preconditioning or control. The authors found that remote ischemic preconditioning reduced acute kidney injury in high-risk patients undergoing cardiac surgery. The authors now report on the effects of remote ischemic preconditioning on 90-day outcomes. METHODS: In this follow-up study of the RenalRIP trial, the authors examined the effect of remote ischemic preconditioning on the composite endpoint major adverse kidney events consisting of mortality, need for renal replacement therapy, and persistent renal dysfunction at 90 days. Secondary outcomes were persistent renal dysfunction and dialysis dependence in patients with acute kidney injury. RESULTS: Remote ischemic preconditioning significantly reduced the occurrence of major adverse kidney events at 90 days (17 of 120 [14.2%]) versus control (30 of 120 [25.0%]; absolute risk reduction, 10.8%; 95% CI, 0.9 to 20.8%; P = 0.034). In those patients who developed acute kidney injury after cardiac surgery, 2 of 38 subjects in the remote ischemic preconditioning group (5.3%) and 13 of 56 subjects in the control group (23.2%) failed to recover renal function at 90 days (absolute risk reduction, 17.9%; 95% CI, 4.8 to 31.1%; P = 0.020). Acute kidney injury biomarkers were also increased in patients reaching the major adverse kidney event endpoint compared to patients who did not. CONCLUSIONS: Remote ischemic preconditioning significantly reduced the 3-month incidence of a composite endpoint major adverse kidney events consisting of mortality, need for renal replacement therapy, and persistent renal dysfunction in high-risk patients undergoing cardiac surgery. Furthermore, remote ischemic preconditioning enhanced renal recovery in patients with acute kidney injury.

The New World Health Organization Recommendations on Perioperative Administration of Oxygen to Prevent Surgical Site Infections: A Dangerous Reductionist Approach?

In October 2016, the World Health Organization (WHO) published recommendations for preventing surgical site infections (SSIs). Among those measures is a recommendation to administer oxygen at an inspired fraction of 80% intra- and postoperatively for up to 6 hours. SSIs have been identified as a global health problem, and the WHO should be commended for their efforts. However, this recommendation focuses only on the patient's "wound," ignores other organ systems potentially affected by hyperoxia, and may ultimately worsen patient outcomes.The WHO advances a "strong recommendation" for the use of a high inspired oxygen fraction even though the quality of evidence is only moderate. However, achieving this goal by disregarding other potentially lethal complications seems inappropriate, particularly in light of the weak evidence underpinning the use of high fractions of oxygen to prevent SSI. Use of such a strategy thus should be intensely discussed by anesthesiologists and perioperative physicians.Normovolemia, normotension, normoglycemia, normothermia, and normoventilation can clearly be safely applied to most patients in most clinical scenarios. But the liberal application of hyperoxemia intraoperatively and up to 6 hours postoperatively, as suggested by the WHO, is questionable from the viewpoint of anesthesia and perioperative medicine, and its effects will be discussed in this article.

Provision of physiological data and reference values in awake and anaesthetized female sheep aged 6-12 months.

OBJECTIVE: To provide physiological data and reference values in awake and anaesthetized sheep aged 6-12 months. STUDY DESIGN: Descriptive study. ANIMALS: Data from 260 female sheep of the species Ovis orientalis aries aged 6-12 months were extracted from 10 experimental trials. METHODS: Data from pulmonary arterial thermodilution in awake (cohort 1; n = 109) and anaesthetized animals (cohort 2; n = 81), and transpulmonary thermodilution in anaesthetized animals (cohort 3; n = 70) were analysed. General anaesthesia was induced by intramuscular injection of S-ketamine and midazolam and maintained by inhaled isoflurane. Standard laboratory variables (blood gas and clinical chemistry) were assessed. RESULTS: A total of 7553 single data entries from 260 healthy sheep were included. Measurement errors or invalid data documentation meant that 313 data entries (4.1%) were excluded. A small confidence interval for median values was calculated for nearly all variables. The median body weight was 39.8 kg (2.5-97.5th percentile 30.6-48.1 kg). A set of reference values (2.5-97.5th percentiles) is provided for common cardiopulmonary and laboratory variables. Compared to awake animals, haemodynamic variables were markedly influenced by anaesthesia, as reflected by a considerably lower stroke volume index in anaesthetized sheep. There were also differences in stroke volume index between the cohorts of pulmonary artery and transpulmonary thermodilution. CONCLUSIONS AND CLINICAL RELEVANCE: The present work presents a large and consistent database of a variety of physiological variables measured in healthy juvenile female sheep. The data appear to be robust and allow the establishment of standardized inclusion criteria for experimental studies and may help to better evaluate past, present and future research. Differences between pulmonary artery and transpulmonary thermodilution should be assessed in future studies.

Patient Blood Management is Associated With a Substantial Reduction of Red Blood Cell Utilization and Safe for Patient's Outcome: A Prospective, Multicenter Cohort Study With a Noninferiority Design.

OBJECTIVE: To determine whether the implementation of patient blood management (PBM) is effective to decrease the use of red blood cell without impairment of patient's safety. BACKGROUND: The World Health Organization encouraged all member states to implement PBM programs employing multiple combined strategies to increase and preserve autologous erythrocyte volume to minimize red blood cell transfusions. Data regarding safety issues are not sufficiently available. METHODS: In this prospective, multicenter study, surgical inpatients from four German University Hospitals were analyzed before (pre-PBM) and after the implementation of PBM. PBM program included multiple measures (ie, preoperative optimization of hemoglobin levels, blood-sparing techniques, and standardization of transfusion practice). Primary aim was to show noninferiority of the PBM cohort with a margin of 0.5%. Secondary endpoints included red blood cell utilization. RESULTS: A total of 129,719 patients discharged between July 2012 and June 2015 with different inclusion periods for pre-PBM (54,513 patients) and PBM (75,206 patients) were analyzed. The primary endpoint was 6.53% in the pre-PBM versus 6.34% in the PBM cohort. The noninferiority aim was achieved (P < 0.001). Incidence of acute renal failure decreased in the PBM cohort (2.39% vs 1.67%; P < 0.001, regression model). The mean number of red blood cell transfused per patient was reduced from 1.21 ±â€Š0.05 to 1.00 ±â€Š0.05 (relative change by 17%, P < 0.001). CONCLUSIONS: The data presented show that implementation of PBM with a more conscious handling of transfusion practice can be achieved even in large hospitals without impairment of patient's safety. Further studies should elucidate which PBM measures are most clinically and cost effective. TRIAL REGISTRATION: PBM-Study ClinicalTrials.gov, NCT01820949.

Synchronized integrin engagement and chemokine activation is crucial in neutrophil extracellular trap-mediated sterile inflammation.

There is emerging evidence that neutrophil extracellular traps (NETs) play important roles in inflammatory processes. Here we report that neutrophils have to be simultaneously activated by integrin-mediated outside-in- and G-protein-coupled receptor (GPCR) signaling to induce NET formation in acute lung injury (ALI), which is associated with a high mortality rate in critically ill patients. NETs consist of decondensed chromatin decorated with granular and cytosolic proteins and they can trap extracellular pathogens. The prerequisite for NET formation is the activation of neutrophils and the release of their DNA. In a neutrophil- and platelet-dependent mouse model of ventilator-induced lung injury (VILI), NETs were found in the lung microvasculature, and circulating NET components increased in the plasma. In this model, blocking integrin-mediated outside-in or either GPCR-signaling or heteromerization of platelet chemokines decreased NET formation and lung injury. Targeting NET components by DNAse1 application or neutrophil elastase-deficient mice protected mice from ALI, whereas DNase1(-/-)/Trap1(m/m) mice had an aggravated ALI, suggesting that NETs directly influence the severity of ALI. These data suggest that NETs form in the lungs during VILI, contribute to the disease process, and thus may be a promising new direction for the treatment of ALI.

Lidocaine reduces neutrophil recruitment by abolishing chemokine-induced arrest and transendothelial migration in septic patients.

The inappropriate activation, positioning, and recruitment of leukocytes are implicated in the pathogenesis of multiple organ failure in sepsis. Although the local anesthetic lidocaine modulates inflammatory processes, the effects of lidocaine in sepsis are still unknown. This double-blinded, prospective, randomized clinical trial was conducted to investigate the effect of lidocaine on leukocyte recruitment in septic patients. Fourteen septic patients were randomized to receive either a placebo (n = 7) or a lidocaine (n = 7) bolus (1.5 mg/kg), followed by continuous infusion (100 mg/h for patients >70 kg or 70 mg/h for patients <70 kg) over a period of 48 h. Selectin-mediated slow rolling, chemokine-induced arrest, and transmigration were investigated by using flow chamber and transmigration assays. Lidocaine treatment abrogated chemokine-induced neutrophil arrest and significantly impaired neutrophil transmigration through endothelial cells by inhibition of the protein kinase C-θ while not affecting the selectin-mediated slow leukocyte rolling. The observed results were not attributable to changes in surface expression of adhesion molecules or selectin-mediated capturing capacity, indicating a direct effect of lidocaine on signal transduction in neutrophils. These data suggest that lidocaine selectively inhibits chemokine-induced arrest and transmigration of neutrophils by inhibition of protein kinase C-θ while not affecting selectin-mediated slow rolling. These findings may implicate a possible therapeutic role for lidocaine in decreasing the inappropriate activation, positioning, and recruitment of leukocytes during sepsis.

Does general anesthesia have a clinical impact on intraocular pressure in children?

BACKGROUND: Reliable measurement of intraocular pressure (IOP) is crucial in pediatric patients with suspected glaucoma. General anesthesia (GA) is usually needed in infants to allow a thorough examination. However, anesthesia itself may influence IOP, depending on the type used and the depth of sedation. The purpose of this study was to evaluate the normal distribution of IOP during GA in healthy children and to analyze differences in IOP relative to the anesthetics used and the measurement time point. METHODS: Approval for this observational study was received from the local institutional review boards and written informed consent was obtained from the children's parents. A total of 100 pediatric patients with no history of glaucoma scheduled for nonintraocular surgery underwent general anesthesia, induced with sevoflurane (s) or propofol (p) and maintained with either sevoflurane with remifentanil (S) or propofol with remifentanil (P). The patients were grouped to one of four subgroups (sS, sP, pP, pS) depending on the anesthetics used during induction and maintenance. Hemodynamic parameters and IOP were measured in both eyes at four defined time points: before anesthesia induction (M1); in apnea immediately after induction and before insertion of a laryngeal mask airway (M2); in deep anesthesia during mechanical ventilation (M3); and after extubation (M4), using a handheld Perkins applanation tonometer. Differences in IOP in both eyes during the measurement periods were analyzed using multivariate repeated-measures analysis of variance and Tukey-HSD as a posthoc test with statistical significance set at P < 0.05. Pearson correlation coefficient was used to investigate further relationships between heart rate, systolic blood pressure, and IOP. RESULTS: General anesthesia reduced IOP significantly. The mean IOP was normally distributed, with a mean of 7.4 ± 2.89 mmHg at M1. It decreased significantly to a minimum of 5.6 ± 3.04 mmHg (P < 0.01) at M2 and increased significantly to 7.2 ± 2.51 mmHg (P < 0.01) at M3 and again to 8.4 ± 3.72 mmHg (P = 0.03) at M4. All four subgroups (sS, sP, pP, pS) showed comparable decreases in IOP between M1 and M2. During deep anesthesia (M3) and during reversal (M4), the IOP increased again in all groups. During reversal (M4), however, the sS group had a significantly lower IOP than the pP group (P = 0.001) and sP group (P = 0.02). There were no correlations between changes in IOP and gender, age, or type of surgery. CONCLUSIONS: Sevoflurane and propofol, both in combination with remifentanil, significantly lower IOP in children. Individual IOP levels rise and fall during anesthesia, depending on the time point of measurement. The lowest IOP can be measured immediately after induction of anesthesia. This needs to be taken into account when measuring IOP in children.

Effect of Early vs Delayed Initiation of Renal Replacement Therapy on Mortality in Critically Ill Patients With Acute Kidney Injury: The ELAIN Randomized Clinical Trial.

IMPORTANCE: Optimal timing of initiation of renal replacement therapy (RRT) for severe acute kidney injury (AKI) but without life-threatening indications is still unknown. OBJECTIVE: To determine whether early initiation of RRT in patients who are critically ill with AKI reduces 90-day all-cause mortality. DESIGN, SETTING, AND PARTICIPANTS: Single-center randomized clinical trial of 231 critically ill patients with AKI Kidney Disease: Improving Global Outcomes (KDIGO) stage 2 (≥2 times baseline or urinary output <0.5 mL/kg/h for ≥12 hours) and plasma neutrophil gelatinase-associated lipocalin level higher than 150 ng/mL enrolled between August 2013 and June 2015 from a university hospital in Germany. INTERVENTIONS: Early (within 8 hours of diagnosis of KDIGO stage 2; n = 112) or delayed (within 12 hours of stage 3 AKI or no initiation; n = 119) initiation of RRT. MAIN OUTCOMES AND MEASURES: The primary end point was mortality at 90 days after randomization. Secondary end points included 28- and 60-day mortality, clinical evidence of organ dysfunction, recovery of renal function, requirement of RRT after day 90, duration of renal support, and intensive care unit (ICU) and hospital length of stay. RESULTS: Among 231 patients (mean age, 67 years; men, 146 [63.2%]), all patients in the early group (n = 112) and 108 of 119 patients (90.8%) in the delayed group received RRT. All patients completed follow-up at 90 days. Median time (Q1, Q3) from meeting full eligibility criteria to RRT initiation was significantly shorter in the early group (6.0 hours [Q1, Q3: 4.0, 7.0]) than in the delayed group (25.5 h [Q1, Q3: 18.8, 40.3]; difference, -21.0 [95% CI, -24.0 to -18.0]; P < .001). Early initiation of RRT significantly reduced 90-day mortality (44 of 112 patients [39.3%]) compared with delayed initiation of RRT (65 of 119 patients [54.7%]; hazard ratio [HR], 0.66 [95% CI, 0.45 to 0.97]; difference, -15.4% [95% CI, -28.1% to -2.6%]; P = .03). More patients in the early group recovered renal function by day 90 (60 of 112 patients [53.6%] in the early group vs 46 of 119 patients [38.7%] in the delayed group; odds ratio [OR], 0.55 [95% CI, 0.32 to 0. 93]; difference, 14.9% [95% CI, 2.2% to 27.6%]; P = .02). Duration of RRT and length of hospital stay were significantly shorter in the early group than in the delayed group (RRT: 9 days [Q1, Q3: 4, 44] in the early group vs 25 days [Q1, Q3: 7, >90] in the delayed group; P = .04; HR, 0.69 [95% CI, 0.48 to 1.00]; difference, -18 days [95% CI, -41 to 4]; hospital stay: 51 days [Q1, Q3: 31, 74] in the early group vs 82 days [Q1, Q3: 67, >90] in the delayed group; P < .001; HR, 0.34 [95% CI, 0.22 to 0.52]; difference, -37 days [95% CI, -∞ to -19.5]), but there was no significant effect on requirement of RRT after day 90, organ dysfunction, and length of ICU stay. CONCLUSIONS AND RELEVANCE: Among critically ill patients with AKI, early RRT compared with delayed initiation of RRT reduced mortality over the first 90 days. Further multicenter trials of this intervention are warranted. TRIAL REGISTRATION: German Clinical Trial Registry Identifier: DRKS00004367.

[Research activities and Graduate Medical Education in Germany]. / Weiterbildung - Forschungstätigkeit und klinische Weiterbildung.

Time spent for research activities can count as time spent in GMA (graduate medical education) as long as requirements according to EU directive 2005/36 concerning minimum time in GMA are fulfilled and the necessary knowledge, experience and competencies have been acquired. First results from a project in Westfalia-Lippe are positive.

[Are subspecialties and fellowship programs in German Anesthesia required?]. / Weiterbildung - Ist eine Subspezialisierung in der Anästhesie erforderlich?

Rapid progress in medical science and technique offer new complex individual treatment modalities. Distinct profile qualifications like echocardiography, electroencephalography are required for anesthesia in high risk populations (cardiovascular, pediatric and neuro surgical patients) to guarantee best patient care and outcome. Accredited subspecialties and distinct fellowship programs are required to improve medical education, training and research.

[Organization of an anaesthesia preoperative evaluation clinic - The Anaesthesia/Patient Blood Management Clinic: one Model]. / Organisation der Prämedikationsambulanz - Die Anästhesie-†/†Patient Blood Management-Sprechstunde: ein Modell.

The anesthesia preoperative evaluation has been developed in recent years in a centralized clinic, that can be visited by the majority of patients, in order to evaluate and obtain patient's consent for anesthesia. In the current article, the organization and structure of such a central anesthesia preoperative evaluation clinic in the Department of Anesthesia, Intensive Care and Pain Medicine at the University Hospital of Muenster, is described. Besides the central preoperative evaluation clinic, 3 clinics are localized in separate buildings and preoperative visits have to be completed in special scenarios on the wards, too. A pharmaceutical evaluation for patient's medication and the patient blood management have been integrated into the anesthesia preoperative evaluation clinic. Processes are explained and current numbers of patients are mentioned.