Prehospital administration of tranexamic acid in trauma patients.

BACKGROUND: Evidence on prehospital administration of the antifibrinolytic tranexamic acid (TXA) in civilian trauma populations is scarce. The aim was to study whether prehospital TXA use in trauma patients was associated with improved outcomes. METHODS: The prehospital database of the ADAC (General German Automobile Club) Air Rescue Service was linked with the TraumaRegister of the German Trauma Society to reidentify patients documented in both registries. Primarily admitted trauma patients (2012 until 2014) who were treated with TXA during the prehospital phase were matched with patients who had not received prehospital TXA, applying propensity score-based matching. RESULTS: The matching yielded two identical cohorts (n = 258 in each group), since there were no significant differences in demographics or injury characteristics (mean Injury Severity Score 24 ± 14 [TXA] vs. 24 ± 16 [control]; p = 0.46). The majority had sustained blunt injury (90.3 % vs. 93.0 %; p = 0.34). There were no differences with respect to prehospital therapy, including rates of intubation, chest tube insertion or both administration of i.v. fluids and catecholamines. During ER treatment, the TXA cohort received fewer numbers of red blood cells and plasma units, but without reaching statistical significance. Incidences of organ failure, sepsis or thromboembolism showed no significant differences as well, although data were incomplete for these parameters. Early mortality was significantly lower in the TXA group (e.g., 24-h mortality 5.8 % [TXA] vs. 12.4 % [control]; p = 0.01), and mean time to death was 8.8 ± 13.4 days vs. 3.6 ± 4.9 days, respectively (p = 0.001). Overall hospital mortality was similar in both groups (14.7 % vs. 16.3 %; p = 0.72). The most pronounced mortality difference was observed in patients with a high propensity score, reflecting severe injury load. CONCLUSIONS: This is the first civilian study, to our knowledge, in which the effect of prehospital TXA use in trauma patients has been examined. TXA was associated with prolonged time to death and significantly improved early survival. Until further evidence emerges, the results of this study support the use of TXA during prehospital treatment of severely injured patients.

Time-resolved crystallography captures light-driven DNA repair.

Photolyase is an enzyme that uses light to catalyze DNA repair. To capture the reaction intermediates involved in the enzyme's catalytic cycle, we conducted a time-resolved crystallography experiment. We found that photolyase traps the excited state of the active cofactor, flavin adenine dinucleotide (FAD), in a highly bent geometry. This excited state performs electron transfer to damaged DNA, inducing repair. We show that the repair reaction, which involves the lysis of two covalent bonds, occurs through a single-bond intermediate. The transformation of the substrate into product crowds the active site and disrupts hydrogen bonds with the enzyme, resulting in stepwise product release, with the 3' thymine ejected first, followed by the 5' base.

Population Dynamics of Stretching Excitations of p-Azido-phenylalanine Incorporated in Calmodulin-Peptide Complexes.

We genetically incorporated the unnatural amino acid p-azido-phenylalanine (AzF) into the ubiquitous Ca2+ sensor protein calmodulin (CaM) in complex with different peptides to explore the response of the azido stretching line shape to varying binding motifs with femtosecond infrared spectroscopy. The dynamic response of the azido stretching mode varies in different CaM-peptide complexes. We model these dynamics as coherent excitations of Fermi resonances and extract a lifetime of the azido stretching vibration of about 1 ps. The resulting model parameters are commensurate with the linear infrared absorption lineshapes which suggests that the conformation-sensitive vibrational lineshape could be composed of Fermi resonances that differ between the protein-peptide complexes.

[Treatment of severely injured patients by emergency physicians from different medical specialties : A retrospective multicenter investigation of data from the ADAC Air Recue Service and the German TraumaRegister DGU®]. / Schwerverletztenversorgung durch Notärzte aus unterschiedlichen Fachgebieten : Eine retrospektive, multizentrische Untersuchung aus Daten der ADAC Luftrettung und des deutschen TraumaRegister DGU®.

BACKGROUND AND OBJECTIVE: The level 3 guidelines on treatment of patients with severe/multiple injuries provide a defined framework for an appropriate treatment of these patients. It is presumed that prehospital diagnostic and therapeutic decisions are affected by the clinical expertise and the medical disciplines of the emergency physicians. METHODS: Retrospective, multicenter study based on data from the ADAC Air Recue Service and the TraumaRegister DGU®. In the study period 2011-2015, a total of 11,019 seriously injured patients were included. They were treated by emergency physicians from the following disciplines: anesthesiology (ANÄ), internal medicine (INN) and surgery (CHIR). RESULTS: Of the patients 81.9% were treated by ANÄ, 7.6% by INN and 10.5% by CHIR. Preclinically, 40.5% of patients were intubated (ANÄ 43.0%, INN 31.2%, CHIR 28.3%; p < 0.001), 5.5% received pleural decompression (ANÄ 5.9%, INN 4.2%, CHIR 2.8%; p = 0.004),and 10.8% were treated with catecholamines (ANÄ 11.3%, INN 8.3%, CHIR 8.3%; p = 0.022). Unconscious patients were intubated in 96.0% (ANÄ 96.1%, INN 97.7%, CHIR 93.9%; p = 0.205). The mortality was not influenced by the medical specialty of the emergency physician. CONCLUSION: In this air rescue cohort differences in indications for invasive procedures were observed between the groups. This may be caused by their clinical background. Using the example of intubation, it has been shown that guideline recommendations were closely followed irrespective of the medical specialty of the emergency physician.

Intraband dynamics of mid-infrared HgTe quantum dots.

Femtosecond pump-probe spectroscopy reveals ultrafast carrier dynamics in mid-infrared (MIR) colloidal HgTe nanoparticles with a bandgap of 2.5 µm. We observe intraband relaxation processes after photoexcitation ranging from resonant excitation up to the multi-exciton generation (MEG) regime by identifying initially excited states from atomic effective pseudopotential calculations. Our study elucidates the earliest dynamics below 10 ps in this technologically relevant material. With increasing photon energy, we find carrier relaxation times as long as 2.1 ps in the MEG regime close to the ionization threshold of the particles. For all photon energies, we extract a constant mean carrier energy dissipation rate of 0.36 eV ps-1 from which we infer negligible impact of the density of states on carrier cooling.

Pre-hospital emergent intubation in trauma patients: the influence of etomidate on mortality, morbidity and healthcare resource utilization.

BACKGROUND: Due to its favorable hemodynamic characteristics and by providing good intubation conditions etomidate is often used for induction of general anesthesia in trauma patients. It has been linked to temporary adrenal cortical dysfunction. The clinical relevance of this finding after a single-dose is still lacking appropriate evidence. METHODS: This retrospective multi-centre study is based on merged data from a German Helicopter Emergency Medical Service (HEMS) database and a large trauma patient registry. All trauma patients who were intubated prior to hospital admission with a documented Injury Severity Score ≥ 9 between 2008 and 2012 were eligible for analysis. The primary endpoint was hospital mortality. Other outcome measures were organ failures, sepsis, length of ventilation, as well as length of stay in hospital and ICU. RESULTS: One thousand six hundred ninety seven patients were enrolled into the study. Seven hundred sixty two patients received etomidate and 935 patients received other induction agents. The in-hospital mortality was similar in both groups (18.9% versus 18.2%; p = 0.71). Incidences of organ failures and sepsis were not increased in the etomidate group. However, health care resource utilization parameters were prolonged (after adjusting: + 1.3 days for ICU length of stay, p = 0.062; + 0.8 days for length of ventilation, p = 0.15; + 2,7 days for hospital length of stay, p = 0.034). A multivariable logistic regression analysis did not identify etomidate as an independent predictor of hospital mortality (OR: 1.10, 95% CI: 0.77-1.57; p = 0.60). CONCLUSIONS: This is the largest trial investigating outcome data for trauma patients who had received a single-dose of etomidate for induction of anesthesia. The use of etomidate did not affect mortality. The influence on morbidity and health care resource utilization remains unclear.

Changes in anaesthetic use for trauma patients in German HEMS - a retrospective study over a ten-year period.

BACKGROUND: Airway management and use of intravenous anaesthetics to facilitate tracheal intubation after major trauma remains controversial. Numerous agents are available and used for pre-hospital rapid-sequence induction (RSI). The aim was to investigate usage and potential changes in administration of intravenous anaesthetics for pre-hospital RSI in trauma patients over a ten-year period. METHODS: Based on a large helicopter emergency medical service (HEMS) database in Germany between 2006 and 2015, a total of 9720 HEMS missions after major trauma leading to RSI on scene were analysed. Administration practice of sedatives and opioids were investigated, while neuromuscular blocking agents were not documented in the database. RESULTS: With respect to administration of sedatives, independent from trauma mechanism and specific injury patterns the use of Etomidate decreased dramatically (52 to 6%) in favour of a more frequent use of Propofol (3 to 32%) and Ketamine (9 to 24%; all p < 0.001) from 2006 to 2015. The use of Benzodiazepines increased slightly, while the utilization rate of Barbiturates remained constant. In patients with Shock Index > 1 at initial contact, the administration rate of Etomidate dropped significantly as well. This decline was mainly substituted by Ketamine and particularly Propofol. In patients with GCS ≤ 8 upon initial contact, a similar distribution compared to the general trauma population could be observed. With respect to opioids, mainly Fentanyl has been administered for RSI in trauma patients (2006: 69,6% to 2015: 60.2%; p < 0.001), while the use of sufentanyl showed a significant increase (0.2 to 8.8%; p < 0.001). CONCLUSIONS: This large study analysed prehospital administration of anaesthetics in trauma patients, showing a substantial change from 2006 to 2015 despite the lack of any high-level evidence. Etomidate has shifted from the main sedative substance to virtual absence, indicating that the recommendation of an established national guideline was transferred into clinical practice, although based on weak evidence as well. The pre-hospital use of Propofol showed a particular increase. Fentanyl has been the main opioid drug for RSI in trauma, however Sufentanyl has become increasingly popular. The mechanisms and advantages of the different substances still have to be elucidated, especially in head injury and bleeding trauma.

EZ-IO(®) intraosseous device implementation in German Helicopter Emergency Medical Service.

BACKGROUND: Intraosseous access (IO) is a rapid and safe alternative when peripheral venous access is difficult. Our aim was to summarize the first three years experience with the use of a semi-automatic IO device (EZ-IO(®)) in German Helicopter Emergency Medical Service (HEMS). METHODS: Included were all patients during study period (January 2009-December 2011) requiring an IO access performed by HEMS team. Outcome variables were IO rate, IO insertion success rates, site of IO access, type of EZ-IO(®) needle set used, strategy of vascular access, procedure related problems and operator's satisfaction. RESULTS: IO rate was 0.3% (348/120.923). Overall success rate was 99.6% with a first attempt success rate of 85.9%; there was only one failure (0.4%). There were three insertion sites: proximal tibia (87.2%), distal tibia (7.5%) and proximal humerus (5.3%). Within total study group IO was predominantly the second-line strategy (39% vs. 61%, p<0.001), but in children<7 years, in trauma cases and in cardiac arrest IO was more often first-line strategy (64% vs. 28%, p<0.001; 48% vs. 34%, p<0.032; 50% vs. 29%, p<0.002 respectively). Patients with IO access were significantly younger (41.7±28.7 vs. 56.5±24.4 years; p<0.001), more often male (63.2% vs. 57.7%; p=0.037), included more trauma cases (37.3% vs. 30.0%; p=0.003) and more often patients with a NACA-Score≥5 rating (77.0% vs. 18.6%; p<0.001). Patients who required IO access generally presented with more severely compromised vital signs associated with the need for more invasive resuscitation actions such as intubation, chest drains, CPR and defibrillation. In 93% EZ-IO(®) needle set handling was rated "good". Problems were reported in 1.6% (needle dislocation 0.8%, needle bending 0.4% and parafusion 0.4%). CONCLUSIONS: The IO route was generally used in the most critically ill of patients. Our relatively low rate of usage would indicate that this would be compatible with the recommendations of established guidelines. The EZ-IO(®) intraosseous device proved feasible with a high success rate in adult and pediatric emergency patients in HEMS.