Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

Anaesthesia in Children and Adolescents with Disabilities

Children and adolescents with disabilities have the right of full and effective participation and inclusion in society. Disability includes a wide range of long-term physical, mental, intellectual and sensory impairments for various reasons. In addition to the basic illness many children with disabilities have concomitant diseases. These diseases are decisive for the perioperative risk. Information from parents regarding their child's behavioural patterns and needs, signs of escalating anxiety and pain are important. Perioperative dialog with the parents is helpful and has positive effects also from parental point of view. Pharmacologic premedication is recommended. Induction of anaesthesia can be challenging and sometimes requires unconventional methods. Pain behaviour may be unusual. There are suitable scales that incorporate such behaviours

A randomized controlled comparison of the Bonfils fiberscope and the GlideScope Cobalt AVL video laryngoscope for visualization of the larynx and intubation of the trachea in infants and small children with normal airways

Background: The Bonfils fiberscope (BF) used without the assistance of a laryngoscope failed to improve the view of direct laryngoscopy in children with normal airways. We hypothesized that if BF is supported by a laryngoscope- as recommended by its inventor-it can provide comparably good visualization of the glottis as the GlideScope (R) Cobalt AVL video laryngoscope (GS). Methods: We included 100 children with normal airways in a randomized controlled trial. The study consisted of assessing the airway by direct laryngoscopy (DL), followed by intubation using either the BF or the GlideScope. Main outcome measures were the quality of visualization of the larynx by the percentage of glottis opening seen (POGO) and the time needed for intubation of the trachea. Results: Visualization of the larynx (POGO) using the BF was significantly better than with DL (P = 0.016) or with GS (P = 0.001). The DL provided an allover better visualization than GS, although this difference was not significant and solely attributable to children weighing <15 kg. Intubation was successful in all cases with both devices. The time needed for intubation was shorter using the BF (36 +/- 8 s) than with the GlideScope (49 +/- 12 s, P < 0.001). Conclusion: The Bonfils fiberscope significantly improved the view on the larynx compared with direc

Novel (imino-&#951;6-arene)chromium-complexes and their diastereoselective intramolecular hetero-Diels-Alder reactions

Novel (imino-&#951;6-arene)chromium complexes 3 with nonactivated olefins tethered to the 2-azadiene system were prepared and further used in a new diastereoselective intramolecular Lewis-acid-catalyzed hetero-Diels-Alder reaction to give (&#951;6-octahydroacridine)chromium complexes 4. The trans selectivity of the cyclization reaction is mainly controlled by the Cr- (CO)3 fragment and to a minor extent by the catalyst, solvent, and substituents. Complexes 4 also could be obtained by a one-pot reaction starting from aldehyde 1, (o-toluidine)Cr(CO)3 (2), and Lewis acid. The stereochemistry of 4a was established by single-crystal X-ray structure analysis

Tracheal intubation with the Bonfils fiberscope in the difficult pediatric airway: a comparison with fiberoptic intubation

BackgroundFiberoptic intubation (FOI) is the gold standard for the tracheal intubation in adults with a difficult airway. However, this technique is more difficult in the narrow pediatric airway and the evaluation of alternative devices in children remains desirable. The Bonfils fiberscope (BF) is well described for the difficult airway, but no clinical data assessing its use in the difficult pediatric airway are available. MethodsA controlled clinical study was conducted comparing BF and FOI in children and infants requiring tracheal intubation with a suspected difficult airway or who demonstrated a difficult airway which was unanticipated. Time to successful intubation, quality of imaging and ease of the intubation procedure were determined. ResultsA total of 26 patients (46% infants) were studied, and all successfully intubated at the first attempt using either the BF or FOI. Mouth opening was restricted in 38% of patients. Time required for intubation was shorter with the BF (5222s) compared with the FOI (83 +/- 24s, P=0.008). The image quality (excellent in 73% vs 45%, P=0.129) and the ease of the procedure (excellent in 67% vs18%, P=0.015) were considered better with BF than with FOI. ConclusionAlthough both the BF and FOI are suitable devices for the intubation of infants and children with difficult airways, the BF may allow faster tracheal intubation with a better image quality and ease of use

Total synthesis and biological evaluation of (-)-pectinatone employing a methyl-branched wax ester as key building block.

Unnatural (-)-pectinatone ((-)-3) was prepared in five steps starting from the highly methyl-branched wax ester 4, employing bromination of the ester enolate and subsequent base-induced elimination to the enoate 6 as the key step. Both (-)-3 and the amides 8b and 8c, which were isolated as by-products in the reaction sequence, displayed antimicrobial activity and cytotoxicity

Development and Prospective Federal State-Wide Evaluation of a Device for Height-Based Dose Recommendations in Prehospital Pediatric Emergencies: A Simple Tool to Prevent Most Severe Drug Errors

Objective: Drug dosing errors pose a particular threat to children in prehospital emergency care. With the Pediatric emergency ruler (PaedER), we developed a simple height-based dose recommendation system and evaluated its effectiveness in a pre-post interventional trial as the Ethics Committee disapproved randomization due to the expected positive effect of the PaedER on outcome. Methods: Pre-interventional data were retrospectively retrieved from the electronic records and medical protocols of the Cologne Emergency Medical Service over a two-year period prior to the introduction of the PaedER. Post-interventional data were collected prospectively over a six-year period in a federal state-wide open trial. The administered doses of either intravenous or intraosseous fentanyl, midazolam, ketamine or epinephrine were recorded. Primary outcome measure was the number and severity of drug dose deviation from recommended dose (DRD) based on the patient's weight. Results: Fifty-nine pre-interventional and 91 post-interventional prehospital drug administrations in children were analyzed. The rate of DRD > 300% overall medications were 22.0% in the pre- and 2.2% in the post-interventional group (p 300%) in pre-interventional and none in post-interventional patients (p < 0.001). Conclusions: The use of the PaedER resulted in a 90% reduction of medication errors (95% CI: 57% to 98%; p < 0.001) and prevented all potentially life-threatening errors associated with epinephrine administration. There is an urgent need to increase the safety of emergency drug dosing in children during emergencies. A simple height-based system can support health care providers and helps to avoid life-threatening medication errors

SAR studies on hydropentalene derivatives--Important core units of biologically active tetramic acid macrolactams and ptychanolides.

Structurally diverse bicyclo[3.3.0]octanes were prepared and tested for their biological activity. Both the antiproliferative activity and the results of phenotypic characterization varied with the substitution patterns. Two derivatives displayed high inhibitory (IC50 ≤3μM) activity against the L-929 cell line, but differed in their mode of action. A cluster analysis with impedance profiling data showed the two compounds in relationship to microtubule interfering compounds. In PtK2 cells treated with both derivatives a perturbing effect on the microtubular network was observed, whereas the actin cytoskeleton in incubated PtK2 cells was disturbed only by one compound. The effects on tubulin and actin polymerization could be confirmed by in vitro polymerization experiments