[Prehospital postcardiac-arrest-sedation and -care in the Federal Republic of Germany-a web-based survey of emergency physicians]. / Präklinische Post-Cardiac-Arrest-Sedierung und -Behandlung in der Bundesrepublik Deutschland ­ eine webbasierte Umfrage unter notärztlichem Personal.

BACKGROUND: This study evaluates the implementation of postcardiac-arrest-sedation (PCAS) and -care (PRC) by prehospital emergency physicians in Germany. MATERIALS AND METHODS: Analysis of a web-based survey from October to November 2022. Questions were asked about implementation, medications used, complications, motivation for implementing or not implementing PCAS, and measures and target parameters of PRC. RESULTS: A total of 500 emergency physicians participated in the survey. In all, 73.4% stated that they regularly performed PCAS (hypnotics: 84.7%; analgesics: 71.1%; relaxants: 29.7%). Indications were pressing against the respirator (88.3%), analgesia (74.1%), synchronization to respirator (59.5%), and change of airway device (52.6%). Reasons for not performing PCAS (26.6%) included unconscious patients (73.7%); concern about hypotension (31.6%), re-arrest (26.3%), and worsening neurological assessment (22.5%). Complications of PCAS were observed by 19.3% of participants (acute hypotension [74.6%]); (re-arrest [32.4%]). In addition to baseline monitoring, PRC included 12-lead-electrocardiogram (96.6%); capnography (91.6%); catecholamine therapy (77.6%); focused echocardiography (20.6%), lung ultrasound (12.0%) and abdominal ultrasound (5.6%); induction of hypothermia (13.6%) and blood gas analysis (7.4%). An etCO2 of 35-45 mm Hg was targeted by 40.6%, while 9.0% of participants targeted an SpO2 of 94-98% and 19.2% of participants targeted a systolic blood pressure of ≥ 100 mm Hg. CONCLUSIONS: Prehospital PRC in Germany is heterogeneous and deviations from its target parameters are frequent. PCAS is frequent and associated with relevant complications. The development of preclinical care algorithms for PCAS and PRC within preclinical care seems urgently needed.

[Introduction of Prehospital Emergency Ultrasound into an Emergency Medical Service Area]. / Einführung der präklinischen Notfallsonographie in einem ländlichen Notarztdienst-Bereich.

BACKGROUND: Emergency ultrasound as part of the provision of emergency medical services using mobile devices offers great benefits regarding to some important questions related to the management of critically ill and injured patients in the prehospital situation where diagnostic resources are limited. The aim of this study is to determine whether the comprehensive introduction of prehospital emergency ultrasound examinations into a German Emergency Medical Services ("rescue services") area is both feasible and beneficial for patients. METHODS: All emergency physicians at a rural emergency physician base were trained in emergency ultrasound scanning techniques (FAST, FEEL, 14 h of instruction), followed by regular weekly training sessions of approximately 30 min. Over a period of 12 months, prehospital ultrasound examinations performed during emergency physician callouts at this base were documented and analysed. RESULTS: A total of 87 emergency ultrasound examinations were performed during 1343 callouts. Among these, focussed assessment with sonography for trauma (FAST) was performed in 35 patients (40.2%) and focused echocardiography in emergency life support (FEEL) in 41 patients (47.1%). In 11 patients (12.6%), ultrasound scans were performed for other indications (e. g. to rule out urinary tract obstruction in a case of flank pain). One trauma patient's life was saved by the decision to transport him to the nearest hospital and once there directly to the operating room, based on the ultrasound finding of significant free intra-abdominal fluid (ruptured spleen and liver). CONCLUSION: Prehospital emergency ultrasound can be introduced into an emergency medical service area as a diagnostic modality that provides benefits to patients. Emergency physicians have to be specifically trained and to participate in continuous education activities. Especially in rural areas with longer transport routes and journey times, the early diagnosis of for example massive intra-abdominal bleeding is critical for the patient's prognosis.

[Point-of-care diagnostics compared to standard coagulation tests in multiple trauma. Pros and cons]. / Point-of-care-Diagnostik vs. Standardlabor beim Polytrauma. Vor- und Nachteile.

The haemostasiological management of patients with multiple injuries requires rapid and adequate therapy decisions due to the highly dynamic surroundings. For this, diagnostic techniques which have the ability to detect and differentiate coagulation disorders that are commonly present in multiple trauma patients are necessary. Widely used routine coagulation tests (e.g., aPTT or PT) sensitively measure impairments of the intrinsic or extrinsic pathway, but without further identification or differentiation. Important influencing parameters like acidosis, hypothermia, fibrinolysis or polymerization dysfunction but especially the clot quality are not detectable. Moreover, the turn around times of these tests are about 30-60 min. However, thrombelastography measures clot strength and stability in whole blood under the present conditions of the injured patient. Impairments of clot quality can be differentiated. Because of the visualization of the clot formation, a patient's coagulation capacity can be assessed within minutes. Admittedly the use of these point-of-care devices in the operation theatre requires human and temporal resources.

[Longitudinal model in pain medicine (LoMoS). Needs assessment and learning developement of learning goals]. / Das longitudinale Modul Schmerzmedizin (LoMoS). Bedarfsanalyse und Lernzielformulierung.

BACKGROUND: Pain medicine as an interdisciplinary, multifaceted field has not yet been assigned the status of a separate medical subject in the curriculum of medical schools in Germany. Pain medicine is often taught by anesthesiologists, neurologists, orthopedic or neurological surgeons either by assignment by the Dean's office or because of their own enthusiasm. In the near future pain medicine as an interdisciplinary course will be mandatory in undergraduate medical education. The authors were interested to investigate the needs and demands of both students and instructors from theoretical and clinical fields in order to develop a longitudinal pain medicine curriculum. METHODS: Based on Kern's curriculum development model, the opinions of students and instructors were investigated: quantitative items were analyzed using Student's t-test for independent variables and heterogenic variance and the content of free text answers was analyzed by forming subsets of similar or identical answers. A concise curriculum was developed. RESULTS: Students from advanced classes noted a bigger discrepancy between the needs formulated and what was actually offered as compared to younger students. Instructors from different theoretical and clinical specialties were unaware of the topics of colleagues from other departments. The analysis of written answers revealed a different understanding of the term pain medicine. CONCLUSION: At the Hannover Medical School, a standardized needs assessment helped to develop LoMoS, the longitudinal pain medicine curriculum, which may also serve as a model for other medical faculties. Students required more practical instruction and teachers were interested in improving networking and discussion among specialists.

Equal effects of gelatin and hydroxyethyl starch (6% HES 130/0.42) on modified thrombelastography in children.

BACKGROUND: Artificial colloids are frequently used to prevent or treat circulatory failure due to hypovolaemia. Whereas gelatin has been shown not to affect coagulation besides its haemodilutional effect, hydroxyethyl starches (HES) have additional negative effects on haemostasis. The third-generation HES solutions have been developed to minimise these effects. We therefore conducted a prospective, randomised study, to verify the hypothesis that a 6% HES 130/0.42/6 : 1 and a 4% gelatin infusion influences modified thrombelastography (TEM) parameters in children in the same manner and to the same extent. METHODS: A total of 50 paediatric patients aged 0-12 years scheduled for surgery were assigned to receive either 10 ml/kg HES 130/0.42 or gelatin. Blood gas analysis, haemodynamic parameters and TEM measurements were performed before and after colloid administration. RESULTS: Patient characteristics, indications/surgical procedures and the main results obtained from blood gas analysis were comparable between the two groups. After administration of either gelatin or HES, all TEM parameters, except for clotting time, indicated impaired coagulation whereas the mean values of all TEM parameters remained within the normal ranges. Comparing the gelatin and HES 130/0.42/6 : 1 groups, none of the measured TEM parameters was found to show between-group differences at baseline or after colloid infusion. CONCLUSION: In conclusion, we could demonstrate that the investigational product, HES 130/0.42/6 : 1 solution, administered at a dosage of 10 ml/kg to children, had comparable effects on coagulation monitored with TEM as a gelatin solution. Perioperative administration of HES 130/0.42/6 : 1 does not alter coagulation to an extent above and beyond the effect of haemodilution.

Specificity of prohormone convertase 2 on proenkephalin and proenkephalin-related substrates.

In the central and peripheral nervous systems, the neuropeptide precursor proenkephalin must be endoproteolytically cleaved by enzymes known as prohormone convertases 1 and 2 (PC1 and PC2) to generate opioid-active enkephalins. In this study, we have investigated the specificity of recombinant mouse PC2 for proenkephalin-related internally quenched (IQ) peptides, for methylcoumarin amide-based fluorogenic peptides, and for recombinant rat proenkephalin. IQ peptides exhibited specificity constants (kcat/Km) between 9.4 x 10(4) M-1 s-1 (Abz-Val-Pro-Arg-Met-Glu-Lys-Arg-Tyr-Gly-Gly-Phe-Met-Gln-EDDnp+ ++; where Abz is ortho-aminobenzoic acid and EDDnp is N-(2, 4-dinitrophenyl)ethylenediamine)) and 0.24 x 10(4) M-1 s-1 (Abz-Tyr-Gly-Gly-Phe-Met-Arg-Arg-Val-Gly-Arg-Pro-Glu-EDDnp), with the peptide B to Met-enk-Arg-Phe cleavage preferred (Met-enk is met-enkephalin). Fluorogenic substrates with P1, P2, and P4 basic amino acids were hydrolyzed with specificity constants ranging between 2.0 x 10(3) M-1 s-1 (Ac-Orn-Ser-Lys-Arg-MCA; where MCA is methylcoumarin amide) and 1.8 x 10(4) M-1 s-1 (

Intestinal uptake of lipovitellin from brine shrimp (Artemia franciscana) by larval inland silversides (Menidia beryllina) and striped bass (Morone saxatilis).

Intestinal uptake of lipovitellin (LV) from brine shrimp (Artemia franciscana) in larval inland silversides (Menidia beryllina) and striped bass (Morone saxatilis) was described using immunocytochemistry. Polyclonal antisera were raised against two subunits of LV (LV68 and LV190). When tested by immunocytochemistry, anti-LV68 showed cross-reactivity with some of the pancreatic cells especially in inland silversides. Therefore anti-LV190 was used to localize immunoreactive LV. Inland silversides at 14 days after hatching were fed Artemia nauplii and then sampled 4, 8, 12 hr after feeding. Similar experiments were carried out by using striped bass at 5 days and 15 days of age. They were sampled at 2, 4, 8, and 12 hr after feeding. Anterior enterocytes showed no evidence of uptake; however, the brush border of the cells of inland silversides reacted with the antiserum. Posterior enterocytes took up the LV and/or, possibly, their immunoreactive breakdown products. The pattern of uptake included accumulation in supranuclear vacuoles and digestion in supranuclear vacuoles, as suggested by the decay of the immunoreactivity over time. Thus, the posterior intestine of these larval fishes is the site of uptake and digestion of LV, an important nutritive component in the food of many larval fishes; this supports earlier findings using non-nutritive marker proteins.

Processing site blockade results in more efficient conversion of proenkephalin to active opioid peptides.

Prohormones are known to be processed at various cleavage sites in a defined temporal order, suggesting the possibility of sequential unfolding of processing sites. In order to investigate whether sequential processing at predefined sites is in fact required for proper processing, site-directed mutagenesis was performed to block known initial cleavage sites within proenkephalin. Pulse-chase/immunoprecipitation experiments were employed to analyze the fate of mutant and native proenkephalins in stably transfected AtT-20 cells. While processing did not occur at blockaded sites, surprisingly, overall processing of mutant proenkephalins proceeded efficiently, and alternative sites were chosen. When compared with native proenkephalin, processing of mutant proenkephalins occurred more slowly at early stages and more quickly at later stages. Experiments employing endoglycosidase H indicated that the early slow processing of mutant proenkephalins may be due to delays in intracellular transport. Metabolic labeling studies showed that more efficient production of bioactive opioids occurred in all processing site blockade mutants examined; these results were confirmed using several different radioimmunoassays of stored peptide products. We conclude that efficient processing of prohormone precursors does not require a specific temporal order of processing events. The fact that mutant proenkephalins were more fully processed than native proenkephalin may provide a route for more efficient production of opioid peptides in applications for chronic pain treatment.

Role of PC2 in proenkephalin processing: antisense and overexpression studies.

The contribution of the prohormone-processing enzyme PC2 to the proteolytic maturation of proenkephalin was examined in three sets of studies. In the first, the processing of this precursor was compared in PC2-rich (Rin5f) and PC2-lacking (AtT-20) cell lines expressing proenkephalin by virtue of stable transfection. These studies showed that the time frame for processing of this precursor is cell line specific, with AtT-20 cells processing proenkephalin to peptide B much more rapidly than Rin cells. However, the latter cell line processed proenkephalin much more extensively, i.e., produced a greater proportion of the penta- to octapeptide enkephalins. The involvement of PC2 in these later processing events was analyzed by examining the processing of proenkephalin in PC2-overexpressing AtT-20 cell lines. These experiments yielded a processing profile similar to that observed for Rin cells, although the time frame of initial processing was similar to that found in AtT-20 cells. To confirm the physiological involvement of proenkephalin in the production of the small opioid peptides, we generated a Rin cell line in which the production of PC2 was impaired due to stable expression of antisense mRNA to this enzyme. These experiments provided conclusive evidence that the generation of Met-enkephalin-Arg-Phe and Met-enkephalin-Arg-Gly-Leu, but not the larger enkephalin-containing peptides, is mediated by PC2. Taken together, our data support the idea that PC2 is physiologically capable of mediating only the later processing steps of neuropeptide precursors. PC2 thus appears to be the primary enzyme responsible for the generation of bioactive opioid peptide species from proenkephalin.