Comparing restrictive versus liberal oxygen strategies for trauma patients: The TRAUMOX2 trial-Statistical analysis plan.

BACKGROUND: The international advanced trauma life support guidelines recommend that all severely injured trauma patients receive supplemental oxygen based on very limited evidence. The TRAUMOX2 trial randomises adult trauma patients to a restrictive or liberal oxygen strategy for 8 h. The primary composite outcome consists of 30-day mortality and/or development of major respiratory complications (pneumonia and/or acute respiratory distress syndrome). This manuscript presents the statistical analysis plan for TRAUMOX2. METHODS: Patients are randomised 1:1 in variable block sizes of four, six and eight, stratified by including centre (pre-hospital base or trauma centre) and tracheal intubation at inclusion. The trial will include 1420 patients to be able to detect a 33% relative risk reduction with the restrictive oxygen strategy of the composite primary outcome with 80% power at the 5% significance level. We will conduct modified intention-to-treat analyses on all randomised patients and per-protocol analyses for the primary composite outcome and key secondary outcomes. The primary composite outcome and two key secondary outcomes will be compared between the two allocated groups using logistic regression reported as odds ratios with 95% confidence intervals adjusted for the stratification variables as in the primary analysis. A p-value below 5% will be considered statistically significant. A Data Monitoring and Safety Committee has been established to conduct interim analyses after inclusion of 25% and 50% of the patients. CONCLUSION: This statistical analysis plan of the TRAUMOX2 trial will minimise bias and add transparency to the statistics applied in the analysis of the trial. The results will add evidence on restrictive and liberal supplemental oxygen strategies for trauma patients. TRIAL REGISTRATION: EudraCT number: 2021-000556-19; ClinicalTrials.gov identifier: NCT05146700 (date of registration: 7 December 2021).

Peri-operative management of neuromuscular blockade: A guideline from the European Society of Anaesthesiology and Intensive Care.

Recent data indicated a high incidence of inappropriate management of neuromuscular block, with a high rate of residual paralysis and relaxant-associated postoperative complications. These data are alarming in that the available neuromuscular monitoring, as well as myorelaxants and their antagonists basically allow well tolerated management of neuromuscular blockade. In this first European Society of Anaesthesiology and Intensive Care (ESAIC) guideline on peri-operative management of neuromuscular block, we aim to present aggregated and evidence-based recommendations to assist clinicians provide best medical care and ensure patient safety. We identified three main clinical questions: Are myorelaxants necessary to facilitate tracheal intubation in adults? Does the intensity of neuromuscular blockade influence a patient's outcome in abdominal surgery? What are the strategies for the diagnosis and treatment of residual paralysis? On the basis of this, PICO (patient, intervention, comparator, outcome) questions were derived that guided a structured literature search. A stepwise approach was used to reduce the number of trials of the initial research ( n  = 24 000) to the finally relevant clinical studies ( n  = 88). GRADE methodology (Grading of Recommendations, Assessment, Development and Evaluation) was used for formulating the recommendations based on the findings of the included studies in conjunction with their methodological quality. A two-step Delphi process was used to determine the agreement of the panel members with the recommendations: R1 We recommend using a muscle relaxant to facilitate tracheal intubation (1A). R2 We recommend the use of muscle relaxants to reduce pharyngeal and/or laryngeal injury following endotracheal intubation (1C). R3 We recommend the use of a fast-acting muscle relaxant for rapid sequence induction intubation (RSII) such as succinylcholine 1 mg kg -1 or rocuronium 0.9 to 1.2 mg kg -1 (1B). R4 We recommend deepening neuromuscular blockade if surgical conditions need to be improved (1B). R5 There is insufficient evidence to recommend deep neuromuscular blockade in general to reduce postoperative pain or decrease the incidence of peri-operative complications. (2C). R6 We recommend the use of ulnar nerve stimulation and quantitative neuromuscular monitoring at the adductor pollicis muscle to exclude residual paralysis (1B). R7 We recommend using sugammadex to antagonise deep, moderate and shallow neuromuscular blockade induced by aminosteroidal agents (rocuronium, vecuronium) (1A). R8 We recommend advanced spontaneous recovery (i.e. TOF ratio >0.2) before starting neostigmine-based reversal and to continue quantitative monitoring of neuromuscular blockade until a TOF ratio of more than 0.9 has been attained. (1C).

Cardiac arrest in the perioperative period: a consensus guideline for identification, treatment, and prevention from the European Society of Anaesthesiology and Intensive Care and the European Society for Trauma and Emergency Surgery.

INTRODUCTION: Cardiac arrest in the operating room is a rare but potentially life-threatening event with mortality rates of more than 50%. Contributing factors are often known, and the event is recognised rapidly as patients are usually under full monitoring. This guideline covers the perioperative period and is complementary to the European Resuscitation Council (ERC) guidelines. MATERIAL AND METHODS: The European Society of Anaesthesiology and Intensive Care and the European Society for Trauma and Emergency Surgery jointly nominated a panel of experts to develop guidelines for the recognition, treatment and prevention of cardiac arrest in the perioperative period. A literature search was conducted in MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials. All searches were restricted to publications from 1980 to 2019 inclusive and to the English, French, Italian and Spanish languages. The authors also contributed individual, independent literature searches. RESULTS: This guideline contains background information and recommendation for the treatment of cardiac arrest in the operating room environment, and addresses controversial topics such as open chest cardiac massage (OCCM), resuscitative endovascular balloon occlusion (REBOA) and resuscitative thoracotomy, pericardiocentesis, needle decompression and thoracostomy. CONCLUSION: Successful prevention and management of cardiac arrest during anaesthesia and surgery requires anticipation, early recognition and a clear treatment plan. The ready availability of expert staff and equipment must also be taken into consideration. Success not only depends on medical knowledge, technical skills and a well organised team using crew resource management but also on an institutional safety culture embedded in everyday practice through continuous education, training and multidisciplinary co-operation.

[Medical emergencies during running events]. / Notfallmedizinische Aspekte bei Laufveranstaltungen.

Background: The number of short- and long-distance running events in Germany is increasing. Running as a popular sport is practiced by a large number of people of different ages, risk groups, and degrees of professionalism, which results in a wide range of medical emergencies. Objective: The present article elucidates incidence, pathophysiology and therapy of relevant emergencies during running events. Aim was the optimization of work processes of emergency personnel. Materials and methods: A literature search was conducted in PubMed. Results: Exercise-associated muscle cramps, gastrointestinal symptoms, collapse, compartment syndrome, and tendinopathy are common clinical manifestations. Cardiac arrest and sudden cardiac death are rare events. Consciousness and seizures are major complications. Disseminated intravascular coagulation, exercise-associated hyponatremia, heat stroke, rhabdomyolysis, and thromboembolism are associated with high morbidity and mortality. Substances increasing pain resilience as well as performance-enhancing substances are popular among amateur and professional runners and are associated with a high incidence of side effects. Conclusion: General symptoms including vomiting, fever, collapse, muscle-pain, nausea and weakness are the leading symptoms during running events. A careful anamnesis is important for targeted clinical therapy. Symptom control is the main task. Fluid management the most challenging task for healthcare providers in the prehospital setting.

Influence of 30 and 60 Min of Hypobaric Hypoxia in Simulated Altitude of 15,000 ft on Human Proteome Profile.

The human body reacts to hypobaric hypoxia, e.g., during a stay at high altitude, with several mechanisms of adaption. Even short-time exposition to hypobaric hypoxia leads to complex adaptions. Proteomics facilitates the possibility to detect changes in metabolism due to changes in proteins. The present study aims to identify time-dependent changes in protein expression due to hypobaric hypoxia for 30 and 60 min at a simulated altitude of 15,000 ft. N = 80 male subjects were randomized and assigned into four different groups: 40 subjects to ground control for 30 (GC30) and 60 min (GC60) and 40 subjects to 15,000 ft for 30 (HH30) and 60 min (HH60). Subjects in HH30 and HH60 were exposed to hypobaric hypoxia in a pressure chamber (total pressure: 572 hPa) equivalent to 15,000 ft for 30 vs. 60 min, respectively. Drawn blood was centrifuged and plasma frozen (-80 °C) until proteomic analysis. After separation of high abundant proteins, protein expression was analyzed by 2-DIGE and MALDI-TOF. To visualize the connected signaling cascade, a bio-informatical network analysis was performed. The present study was approved by the ethical committee of the University of Cologne, Germany. The study registry number is NCT03823677. In comparing HH30 to GC30, a total of seven protein spots had a doubled expression, and 22 spots had decreased gene expression. In a comparison of HH60 to GC60, a total of 27 protein spots were significantly higher expressed. HH60, as compared to GC30, revealed that a total of 37 spots had doubled expression. Vice versa, 12 spots were detected, which were higher expressed in GC30 vs. HH60. In comparison to GC, HH60 had distinct differences in the number of differential protein spots (noticeably more proteins due to longer exposure to hypoxia). There are indicators that changes in proteins are dependent on the length of hypobaric hypoxia. Some proteins associated with hemostasis were differentially expressed in the 60 min comparison.

Rapid Downregulation of H3K4me3 Binding to Immunoregulatory Genes in Altered Gravity in Primary Human M1 Macrophages.

The sensitivity of human immune system cells to gravity changes has been investigated in numerous studies. Human macrophages mediate innate and thus rapid immune defense on the one hand and activate T- and B-cell-based adaptive immune response on the other hand. In this process they finally act as immunoeffector cells, and are essential for tissue regeneration and remodeling. Recently, we demonstrated in the human Jurkat T cell line that genes are differentially regulated in cluster structures under altered gravity. In order to study an in vivo near system of immunologically relevant human cells under physically real microgravity, we performed parabolic flight experiments with primary human M1 macrophages under highly standardized conditions and performed chromatin immunoprecipitation DNA sequencing (ChIP-Seq) for whole-genome epigenetic detection of the DNA-binding loci of the main transcription complex RNA polymerase II and the transcription-associated epigenetic chromatin modification H3K4me3. We identified an overall downregulation of H3K4me3 binding loci in altered gravity, which were unequally distributed inter- and intrachromosomally throughout the genome. Three-quarters of all affected loci were located on the p arm of the chromosomes chr5, chr6, chr9, and chr19. The genomic distribution of the downregulated H3K4me3 loci corresponds to a substantial extent to immunoregulatory genes. In microgravity, analysis of RNA polymerase II binding showed increased binding to multiple loci at coding sequences but decreased binding to central noncoding regions. Detection of altered DNA binding of RNA polymerase II provided direct evidence that gravity changes can lead to altered transcription. Based on this study, we hypothesize that the rapid transcriptional response to changing gravitational forces is specifically encoded in the epigenetic organization of chromatin.

Time to ventilation and success rate of airway devices in microgravity: A randomized crossover manikin-trial using an underwater setting.

BACKGROUND: Medical support for space exploration missions must prepare for severe medical events in conditions of microgravity. A key component to managing these events is techniques of airway management. The aim of the present trial is to compare airway management devices in simulated microgravity. METHODS: In this randomized cross-over trial (RCT), four different devices were compared under simulated microgravity conditions utilizing a neutrally buoyant free-floating underwater manikin and poolside in normal gravity (control group). The primary endpoint was the successful placement of the airway device. The secondary endpoints were the number of attempts and the duration of each attempt. RESULTS: A total of 20 participants performed placement of each device in both gravity conditions in an Airway mannequin. The fastest time to initial ventilation in simulated microgravity was possible with the laryngeal tube (18.9 ± 8 seconds) followed by laryngeal mask (20.1 ± 9 seconds). The I-gel® supraglottic airway device required substantially more time for successful insertion in simulated microgravity (35.4 ± 25 seconds) as did endotracheal tube intubation by direct laryngoscopy (70.4 ± 35 seconds). Simulated microgravity conditions prolonged time to initial ventilation by 3.3 seconds (LM), 3.9 seconds (LT), 19.9 seconds (I-gel) and 43.1 seconds (endotracheal intubation, ETI) when compared to poolside attempts in normogravity. CONCLUSION: In simulated microgravity conditions, use of the laryngeal tube or laryngeal mask provided the quickest time to initial ventilation, without deliberate tethering of the mannequin and rescuer to a fixed surface. Endotracheal intubation required significantly longer procedure times and, thus, was considered insufficient for clinical use in microgravity.

Verbal Motivation vs. Digital Real-Time Feedback during Cardiopulmonary Resuscitation: Comparing Bystander CPR Quality in a Randomized and Controlled Manikin Study of Simulated Cardiac Arrest.

OBJECTIVE: The use of smartphone applications increases bystander CPR quality as well as the use of telephone CPR protocols. The present prospective, randomized, controlled manikin trial analyses the effects of a smartphone application (PocketCPR©) on CPR quality in a bystander CPR scenario compared to a dispatcher-assisted telephone CPR with the additional use of a metronome and verbal motivation. Methods: 150 laypersons were included to perform 8-minute CPR on a manikin. Volunteers were randomly assigned to one of three groups: (1) dispatcher-assisted telephone CPR (telephone-group), (2) dispatcher-assisted telephone CPR combined with the smartphone-application (telephone + app-group) and (3) dispatcher-assisted telephone CPR with additional verbal motivation ("push harder, release completely," every 20 seconds, starting after 60 seconds) and a metronome with 100 min-1 (telephone + motivation-group). Results: Median compression depth did not differ significantly between the study groups (p = 0.051). However, in the post hoc analysis median compression depth in the telephone + motivation-group was significantly elevated compared to the telephone + app-group (59 mm [IQR 47-67 mm] vs. 51 mm [IQR 46-57 mm]; p = 0.025). The median number of superficial compressions was significantly reduced in the telephone + motivation-group compared to the telephone + app-group (70 [IQR 3-362] vs. 349 [IQR 88-538]; p = 0.004), but not compared to the telephone-group (91 [IQR 4-449]; p = 0.707). In contrast to the other study groups, median compression depth of the telephone + motivation-group increased over time. Chest compressions with correct depth were found significantly more often in the telephone + app-group compared to the other study groups (p = 0.011). Median compression rate in the telephone + app-group was significantly elevated (108 min-1 [IQR 96-119 min-1]) compared to the telephone-group (78 min-1 [IQR 56-106 min-1]; p < 0.001) and the telephone + motivation-group (99 min-1 [IQR 91-101 min-1]; p < 0.001). Conclusions: The use of a smartphone application as well as verbal motivation by a dispatcher during telephone CPR leads to higher CPR quality levels compared to standard telephone CPR. Thereby, the use of the smartphone application mainly shows an increase in compression rate, while increased compression rate with simultaneously increased compression depth was only apparent in the telephone + motivation-group.

[Cardiac arrest under special circumstances]. / Kreislaufstillstand unter besonderen Umständen: Leitlinien des European Resuscitation Council 2021.

These guidelines of the European Resuscitation Council (ERC) Cardiac Arrest under Special Circumstances are based on the 2020 International Consensus on Cardiopulmonary Resuscitation Science with Treatment Recommendations. This section provides guidelines on the modifications required for basic and advanced life support for the prevention and treatment of cardiac arrest under special circumstances; in particular, specific causes (hypoxia, trauma, anaphylaxis, sepsis, hypo-/hyperkalaemia and other electrolyte disorders, hypothermia, avalanche, hyperthermia and malignant hyperthermia, pulmonary embolism, coronary thrombosis, cardiac tamponade, tension pneumothorax, toxic agents), specific settings (operating room, cardiac surgery, cardiac catheterization laboratory, dialysis unit, dental clinics, transportation [in-flight, cruise ships], sport, drowning, mass casualty incidents), and specific patient groups (asthma and chronic obstructive pulmonary disease, neurological disease, morbid obesity, pregnancy).

Procedural sedation outside the operating room.

PURPOSE OF REVIEW: The present review provides an overview of the different fields of procedural sedation and analgesia (PSA), describing the evidence from recently published studies concerning anxiety and moderate pain, cardiac interventions, gastrointestinal interventions, and PSA use in infants. It also provides guidance for practitioners of both unscheduled and scheduled procedural sedation, and a summary of the current guideline for PSA. RECENT FINDINGS: Safety always has to be first priority. Recently published literature is focusing on the combination of different well established drugs such as dexmedetomidine, remifentanil, propofol, and ketamine. These traditional and well known drugs are commonly used for PSA. The combinational use of multiple drugs seems to have benefits for both the provider and patient. Furthermore, there is growing interest into specific protocols and adaption for special circumstances. The preferred medications used for PSA should be both effective and well tolerated. SUMMARY: Procedural sedation deserves to have high degree of attention for potential adverse events. New combinations of well established drugs provide a better pharmacokinetic profile, fit to different indications and offer multiple benefits for both provider and patient.

Airway management in microgravity: A systematic review.

INTRODUCTION: In the near future, space programs will shift their focus toward long-duration interplanetary missions, in particular to the Moon and Mars. These exploration missions will be associated with an increased risk of acute medical problems, which will need to be handled by an autonomous crew operating in extreme isolation. An important skill in emergencies is represented by airway management. Many airway devices are available and it is unclear which one would be the most suitable in the context of a space mission. The aim of this systematic review was to analyze the existing literature on airway management in the special situation of weightlessness during space missions. MATERIAL AND METHODS: We performed a standardized review of published literature on airway management in spaceflight and analogue environments using the database PubMed. RESULTS: We identified a total of 3111 publications of which 3039 were initially excluded after evaluation. The screening identified three randomized comparative manikin studies, two of them in parabolic flights, one in a submerged setup. Under free-floating conditions, the insertion success rate of supraglottic airway devices (SGA) was excellent (91%-97%). The administration of artificial ventilation could be successfully achieved in weightlessness with SGA. The success rate of conventional laryngoscopy under free-floating conditions fluctuated between 15% and 86%. CONCLUSION: It appears possible to safely manage the airway in weightlessness, provided that certain conditions are ensured, such as restraining the patient and operator for conventional orotracheal intubation. If airway protection is required with endotracheal intubation, both the operator and the patient should be restrained.

Outcomes in video laryngoscopy studies from 2007 to 2017: systematic review and analysis of primary and secondary endpoints for a core set of outcomes in video laryngoscopy research.

BACKGROUND: Airway management is crucial and, probably, even the most important key competence in anaesthesiology, which directly influences patient safety and outcome. However, high-quality research is rarely published and studies usually have different primary or secondary endpoints which impedes clear unbiased comparisons between studies. The aim of the present study was to gather and analyse primary and secondary endpoints in video laryngoscopy studies being published over the last ten years and to create a core set of uniform or homogeneous outcomes (COS). METHODS: Retrospective analysis. Data were identified by using MEDLINE® database and the terms "video laryngoscopy" and "video laryngoscope" limited to the years 2007 to 2017. A total of 3351 studies were identified by the applied search strategy in PubMed. Papers were screened by two anaesthesiologists independently to identify study endpoints. The DELPHI method was used for consensus finding. RESULTS: In the 372 studies analysed and included, 49 different outcome categories/columns were reported. The items "time to intubation" (65.86%), "laryngeal view grade" (44.89%), "successful intubation rate" (36.56%), "number of intubation attempts" (23.39%), "complications" (21.24%), and "successful first-pass intubation rate" (19.09%) were reported most frequently. A total of 19 specific parameters is recommended. CONCLUSIONS: In recent video laryngoscopy studies, many different and inhomogeneous parameters were used as outcome descriptors/endpoints. Based on these findings, we recommend that 19 specific parameters (e.g., "time to intubation" (inserting the laryngoscope to first ventilation), "laryngeal view grade" (C&L and POGO), "successful intubation rate", etc.) should be used in coming research to facilitate future comparisons of video laryngoscopy studies.

Incidence of peri-operative paediatric cardiac arrest and the influence of a specialised paediatric anaesthesia team: Retrospective cohort study.

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

European Society of Anaesthesiology and European Board of Anaesthesiology guidelines for procedural sedation and analgesia in adults.

: Procedural sedation and analgesia (PSA) has become a widespread practice given the increasing demand to relieve anxiety, discomfort and pain during invasive diagnostic and therapeutic procedures. The role of, and credentialing required by, anaesthesiologists and practitioners performing PSA has been debated for years in different guidelines. For this reason, the European Society of Anaesthesiology (ESA) and the European Board of Anaesthesiology have created a taskforce of experts that has been assigned to create an evidence-based guideline and, whenever the evidence was weak, a consensus amongst experts on: the evaluation of adult patients undergoing PSA, the role and competences required for the clinicians to safely perform PSA, the commonly used drugs for PSA, the adverse events that PSA can lead to, the minimum monitoring requirements and post-procedure discharge criteria. A search of the literature from 2003 to 2016 was performed by a professional librarian and the retrieved articles were analysed to allow a critical appraisal according to the Grading of Recommendations Assessment, Development and Evaluation method. The Taskforce selected 2248 articles. Where there was insufficiently clear and concordant evidence on a topic, the Rand Appropriateness Method with three rounds of Delphi voting was used to obtain the highest level of consensus among the taskforce experts.These guidelines contain recommendations on PSA in the adult population. It does not address sedation performed in the ICU or in children and it does not aim to provide a legal statement on how PSA should be performed and by whom. The National Societies of Anaesthesiology and Ministries of Health should use this evidence-based document to help decision-making on how PSA should be performed in their countries. The final draft of the document was available to ESA members via the website for 4 weeks with the facility for them to upload their comments. Comments and suggestions of individual members and national Societies were considered and the guidelines were amended accordingly. The ESA guidelines Committee and ESA board finally approved and ratified it before publication.

Pre-operative evaluation of adults undergoing elective noncardiac surgery: Updated guideline from the European Society of Anaesthesiology.

: The purpose of this update of the European Society of Anaesthesiology (ESA) guidelines on the pre-operative evaluation of the adult undergoing noncardiac surgery is to present recommendations based on the available relevant clinical evidence. Well performed randomised studies on the topic are limited and therefore many recommendations rely to a large extent on expert opinion and may need to be adapted specifically to the healthcare systems of individual countries. This article aims to provide an overview of current knowledge on the subject with an assessment of the quality of the evidence in order to allow anaesthesiologists all over Europe to integrate - wherever possible - this knowledge into daily patient care. The Guidelines Committee of the ESA formed a task force comprising members of the previous task force, members of ESA scientific subcommittees and an open call for volunteers was made to all individual active members of the ESA and national societies. Electronic databases were searched from July 2010 (end of the literature search of the previous ESA guidelines on pre-operative evaluation) to May 2016 without language restrictions. A total of 34 066 abtracts were screened from which 2536 were included for further analysis. Relevant systematic reviews with meta-analyses, randomised controlled trials, cohort studies, case-control studies and cross-sectional surveys were selected. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to assess the level of evidence and to grade recommendations. The final draft guideline was posted on the ESA website for 4 weeks and the link was sent to all ESA members, individual or national (thus including most European national anaesthesia societies). Comments were collated and the guidelines amended as appropriate. When the final draft was complete, the Guidelines Committee and ESA Board ratified the guidelines.

Time Dependent Pathway Activation of Signalling Cascades in Rat Organs after Short-Term Hyperoxia.

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

[Rapid Sequence Induction]. / Rapid Sequence Induction.

A Rapid Sequence Induction and Intubation (RSI oder RSII) is a standard technique for emergency airway management and anaesthesia. The aim of an RSI is to prevent aspiration by fast endotracheal intubation without the use of facemask ventilation.Today, only few European countries have specific guidelines for RSI. During daily practice, head-up positioning is standard and provides some advantages as compared to other positions. A gastric tube should be left in place; it is not necessary to remove it. If no gastric tube is in place, it can be positioned after intubation. An opioid should be administered prior to RSI since it may reduce the dosage of the hypnotic drug and, therefore, side effects, too.

Transcutaneous PTCCO2 measurement in combination with arterial blood gas analysis provides superior accuracy and reliability in ICU patients.

Hyper or hypoventilation may have serious clinical consequences in critically ill patients and should be generally avoided, especially in neurosurgical patients. Therefore, monitoring of carbon dioxide partial pressure by intermittent arterial blood gas analysis (PaCO2) has become standard in intensive care units (ICUs). However, several additional methods are available to determine PCO2 including end-tidal (PETCO2) and transcutaneous (PTCCO2) measurements. The aim of this study was to compare the accuracy and reliability of different methods to determine PCO2 in mechanically ventilated patients on ICU. After approval of the local ethics committee PCO2 was determined in n = 32 ICU consecutive patients requiring mechanical ventilation: (1) arterial PaCO2 blood gas analysis with Radiometer ABL 625 (ABL; gold standard), (2) arterial PaCO2 analysis with Immediate Response Mobile Analyzer (IRMA), (3) end-tidal PETCO2 by a Propaq 106 EL monitor and (4) transcutaneous PTCCO2 determination by a Tina TCM4. Bland-Altman method was used for statistical analysis; p < 0.05 was considered statistically significant. Statistical analysis revealed good correlation between PaCO2 by IRMA and ABL (R2 = 0.766; p < 0.01) as well as between PTCCO2 and ABL (R2 = 0.619; p < 0.01), whereas correlation between PETCO2 and ABL was weaker (R2 = 0.405; p < 0.01). Bland-Altman analysis revealed a bias and precision of 2.0 ± 3.7 mmHg for the IRMA, 2.2 ± 5.7 mmHg for transcutaneous, and -5.5 ± 5.6 mmHg for end-tidal measurement. Arterial CO2 partial pressure by IRMA (PaCO2) and PTCCO2 provided greater accuracy compared to the reference measurement (ABL) than the end-tidal CO2 measurements in critically ill in mechanically ventilated patients patients.

Thirty Minutes of Hypobaric Hypoxia Provokes Alterations of Immune Response, Haemostasis, and Metabolism Proteins in Human Serum.

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