Perioperative use of oxygen: variabilities across age

Enormous interest has emerged in the perioperative use of high concentrations of inspired oxygen in an attempt to increase tissue oxygenation and thereby improve postoperative outcome. An extensive debate has arisen regarding the risk/benefit ratio of oxygen therapy, with some researchers advocating the benefits of perioperative hyperoxia, particularly with regard to surgical site infection, whereas others emphasize its detrimental consequences on multiple organs, particularly the lungs and the brain. As one aspect of this debate, there is increased awareness of effects of reactive oxygen metabolites, a feature that contributes to the complexity of achieving consensus regarding optimum oxygen concentration in the perioperative period. Many reviews have discussed the pros and cons in the use of perioperative oxygen supplementation, but the potential importance of age-related factors in hyperoxia has not been addressed. The present narrative review provides a comprehensive overview of the physiological mechanisms and clinical outcomes across the age range from neonates to the elderly. Risks greatly outweigh the benefits of hyperoxia both in the very young, where growth and development are the hallmarks, and in the elderly, where ageing increases sensitivity to oxidative stress. Conversely, in middle age, benefits of short-term administration of perioperative oxygen therapy exceed potential adverse change effects, and thus, oxygen supplementation can be considered an important therapy to improve anaesthesia managemen

Effects of volatile anaesthetic agents on enhanced airway tone in sensitized guinea pigs

Background. Although volatile anaesthetics afford protection against bronchospasm, their potential to reverse a sustained constriction of hyperreactive airways has not been characterized. Accordingly, we investigated the ability of halothane, isoflurane, sevoflurane and desflurane to reverse lung constriction induced by prolonged stimulation of the muscarinic receptors in guinea pigs sensitized to ovalbumin. Methods. Pulmonary input impedance (ZL) was measured using forced oscillations in five groups of ovalbumin‐sensitized, mechanically ventilated guinea pigs. ZL was measured under baseline conditions, during steady‐state bronchoconstriction induced by an i.v. infusion of methacholine (MCh), and after administration of one of the volatile agents at 1 MAC after the induction of a steady‐state bronchoconstriction. Airway resistance (Raw), and parenchymal tissue resistive and elastic coefficients were extracted from ZL by model fitting. Results. All four volatile agents exhibited an initial relaxation of the MCh‐induced airway constriction followed by gradual increases in Raw. The bronchodilatory effect of isoflurane was the most potent (-28.9 (se 5.5)% at 2 min, P<0.05) and lasted longest (7 min); sevoflurane and halothane had shorter and more moderate effects (-21.1 (3.9)%, P<0.05, and -6.1 (1.7)%, P<0.05, respectively, at 1 min). Desflurane caused highly variable changes in Raw, with a tendency to enhance airway tone. Conclusions. Volatile agents can reverse sustained MCh‐induced airway constriction only transiently in sensitized guinea pigs. Isoflurane proved most beneficial in temporally improving lung function in the presence of a severe constriction of allergic inflamed airways. Desflurane displayed potential to induce further airway constriction. Br J Anaesth 2004; 92: 254-6

MHC class II complexes sample intermediate states along the peptide exchange pathway

The presentation of peptide-MHCII complexes (pMHCIIs) for surveillance by T cells is a well-known immunological concept in vertebrates, yet the conformational dynamics of antigen exchange remain elusive. By combining NMR- detected H/D exchange with Markov modelling analysis of an aggregate of 275 microseconds molecular dynamics simulations, we reveal that a stable pMHCII spontaneously samples intermediate conformations relevant for peptide exchange. More specifically, we observe two major peptide exchange pathways: the kinetic stability of a pMHCII’s ground state defines its propensity for intrinsic peptide exchange, while the population of a rare, intermediate conformation correlates with the propensity of the HLA-DM-catalysed pathway. Helix-destabilizing mutants designed based on our model shift the exchange behaviour towards the HLA-DM-catalysed pathway and further allow us to conceptualize how allelic variation can shape an individual’s MHC restricted immune response

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

Does implicit memory during anaesthesia persist in children?

Background Recent studies suggest that implicit memory (especially perceptual implicit memory) persists during adequate general anaesthesia in adults. Studies in children, however, have failed to demonstrate implicit memory during general anaesthesia, possibly because of differences in methodological design. We therefore designed a prospective study with the aim of evaluating implicit memory in children undergoing general anaesthesia, using a perceptual memory test based on the mere exposure effect, previously tested in a control group. Methods Twelve infrequent neutral words were played 12 times in a random sequence via headphones to 36 children aged 8-12 yr during elective or emergency surgery. The children were not premedicated, and general anaesthesia was maintained with isoflurane. The word presentation started immediately after the surgical incision. Within 36 h after the stimulus presentation, the memory was assessed by using a forced-choice preference judgement task. Time constraint and word deterioration with a low-pass filter were used to prevent the subjects from utilizing intentional retrieval. The implicit memory score was obtained by calculating the proportion of target words preferred, which was compared with the chance level (0.5). Results The percentage of correct responses given by the children was comparable with the chance level. The memory score was mean (sd) 0.48 (0.16) (95% CI 0.43-0.53). Conclusions The use of a perceptual implicit memory test based on the mere exposure procedure in children failed to reveal any evidence of implicit memory under general anaesthesi

Students’ Evolving Meaning About Tangent Line with the Mediation of a Dynamic Geometry Environment and an Instructional Example Space

In this paper I report a lengthy episode from a teaching experiment in which fifteen Year 12 Greek students negotiated their definitions of tangent line to a function graph. The experiment was designed for the purpose of introducing students to the notion of derivative and to the general case of tangent to a function graph. Its design was based on previous research results on students’ perspectives on tangency, especially in their transition from Geometry to Analysis. In this experiment an instructional example space of functions was used in an electronic environment utilising Dynamic Geometry software with Function Grapher tools. Following the Vygotskian approach according to which students’ knowledge develops in specific social and cultural contexts, students’ construction of the meaning of tangent line was observed in the classroom throughout the experiment. The analysis of the classroom data collected during the experiment focused on the evolution of students’ personal meanings about tangent line of function graph in relation to: the electronic environment; the pre-prepared as well as spontaneous examples; students’ engagement in classroom discussion; and, the role of researcher as a teacher. The analysis indicated that the evolution of students’ meanings towards a more sophisticated understanding of tangency was not linear. Also it was interrelated with the evolution of the meaning they had about the inscriptions in the electronic environment; the instructional example space; the classroom discussion; and, the role of the teacher

Radiological findings of complications after lung transplantation.

Complications following lung transplantation may impede allograft function and threaten patient survival. The five main complications after lung transplantation are primary graft dysfunction, post-surgical complications, alloimmune responses, infections, and malignancy. Primary graft dysfunction, a transient ischemic/reperfusion injury, appears as a pulmonary edema in almost every patient during the first three days post-surgery. Post-surgical dysfunction could be depicted on computed tomography (CT), such as bronchial anastomosis dehiscence, bronchial stenosis and bronchomalacia, pulmonary artery stenosis, and size mismatch. Alloimmune responses represent acute rejection or chronic lung allograft dysfunction (CLAD). CLAD has three different forms (bronchiolitis obliterans syndrome, restrictive allograft syndrome, acute fibrinoid organizing pneumonia) that could be differentiated on CT. Infections are different depending on their time of occurrence. The first post-operative month is mostly associated with bacterial and fungal pathogens. From the second to sixth months, viral pneumonias and fungal and parasitic opportunistic infections are more frequent. Different patterns according to the type of infection exist on CT. Malignancy should be depicted and corresponded principally to post-transplantation lymphoproliferative disease (PTLD). In this review, we describe specific CT signs of these five main lung transplantation complications and their time of occurrence to improve diagnosis, follow-up, medical management, and to correlate these findings with pathology results. KEY POINTS: • The five main complications are primary graft dysfunction, surgical, alloimmune, infectious, and malignancy complications. • CT identifies anomalies in the setting of unspecific symptoms of lung transplantation complications. • Knowledge of the specific CT signs can allow a prompt diagnosis. • CT signs maximize the yield of bronchoscopy, transbronchial biopsy, and bronchoalveolar lavage. • Radiopathological correlation helps to understand CT signs after lung transplantation complications

Prevention of bronchial hyperreactivity in a rat model of precapillary pulmonary hypertension

<p>Abstract</p> <p>Background</p> <p>The development of bronchial hyperreactivity (BHR) subsequent to precapillary pulmonary hypertension (PHT) was prevented by acting on the major signalling pathways (endothelin, nitric oxide, vasoactive intestine peptide (VIP) and prostacyclin) involved in the control of the pulmonary vascular and bronchial tones.</p> <p>Methods</p> <p>Five groups of rats underwent surgery to prepare an aorta-caval shunt (ACS) to induce sustained precapillary PHT for 4 weeks. During this period, no treatment was applied in one group (ACS controls), while the other groups were pretreated with VIP, iloprost, tezosentan via an intraperitoneally implemented osmotic pump, or by orally administered sildenafil. An additional group underwent sham surgery. Four weeks later, the lung responsiveness to increasing doses of an intravenous infusion of methacholine (2, 4, 8 12 and 24 μg/kg/min) was determined by using the forced oscillation technique to assess the airway resistance (Raw).</p> <p>Results</p> <p>BHR developed in the untreated rats, as reflected by a significant decrease in ED₅₀, the equivalent dose of methacholine required to cause a 50% increase in Raw. All drugs tested prevented the development of BHR, iloprost being the most effective in reducing both the systolic pulmonary arterial pressure (Ppa; 28%, p = 0.035) and BHR (ED₅₀= 9.9 ± 1.7 vs. 43 ± 11 μg/kg in ACS control and iloprost-treated rats, respectively, p = 0.008). Significant correlations were found between the levels of Ppa and ED₅₀(R = -0.59, p = 0.016), indicating that mechanical interdependence is primarily responsible for the development of BHR.</p> <p>Conclusions</p> <p>The efficiency of such treatment demonstrates that re-establishment of the balance of constrictor/dilator mediators via various signalling pathways involved in PHT is of potential benefit for the avoidance of the development of BHR.</p

Ambient air pollutants are associated with morning serum cortisol in overweight and obese Latino youth in Los Angeles

Background Hypothalamic-pituitary-adrenal (HPA)-axis dysfunction has been associated with a variety of mental health and cardio-metabolic disorders. While causal models of HPA-axis dysregulation have been largely focused on either pre-existing health conditions or psychosocial stress factors, recent evidence suggests a possible role for central nervous system activation via air pollutants, such as nitrogen dioxide (NO2), ozone (O3) and particulate matter (PM). Therefore, in an observational study of Latino youth, we investigated if monthly ambient NO2, O3, and PM with aerodynamic diameter&thinsp;&le;&thinsp;2.5 (PM2.5) exposure were associated with morning serum cortisol levels. Methods In this cross-sectional study, morning serum cortisol level was assessed after a supervised overnight fast in 203 overweight and obese Latino children and adolescents (female/male: 88/115; mean age: 11.1&thinsp;&plusmn;&thinsp;1.7&thinsp;years; pre-pubertal/pubertal/post-pubertal: 85/101/17; BMI z-score: 2.1&thinsp;&plusmn;&thinsp;0.4). Cumulative concentrations of NO2, O3 and PM2.5 were spatially interpolated at the residential addresses based on measurements from community monitors up to 12&thinsp;months prior to testing. Single and multi-pollutant linear effects models were used to test the cumulative monthly lag effects of NO2, O3, and PM2.5 on morning serum cortisol levels after adjusting for age, sex, seasonality, social position, pubertal status, and body fat percent by DEXA. Results Single and multi-pollutant models showed that higher O3 exposure (derived from maximum 8-h exposure windows) in the prior 1&ndash;7&thinsp;months was associated with higher serum morning cortisol (p&thinsp;&lt;&thinsp;0.05) and longer term PM2.5 exposure (4&ndash;10&thinsp;months) was associated with lower serum morning cortisol levels (p&thinsp;&lt;&thinsp;0.05). Stratification by pubertal status showed associations in pre-pubertal children compared to pubertal and post-pubertal children. Single, but not multi-pollutant, models showed that higher NO2 over the 4&ndash;10&thinsp;month exposure period associated with lower morning serum cortisol (p&thinsp;&lt;&thinsp;0.05). Conclusions Chronic ambient NO2, O3 and PM2.5 differentially associate with HPA-axis dysfunction, a mechanism that may serve as an explanatory pathway in the relationship between ambient air pollution and metabolic health of youth living in polluted urban environments. Further research that uncovers how ambient air pollutants may differentially contribute to HPA-axis dysfunction are warranted. </div

Airway management in neonates and infants: European Society of Anaesthesiology and Intensive Care and British Journal of Anaesthesia joint guidelines.

Airway management is required during general anaesthesia and is essential for life-threatening conditions such as cardiopulmonary resuscitation. Evidence from recent trials indicates a high incidence of critical events during airway management, especially in neonates or infants. It is important to define the optimal techniques and strategies for airway management in these groups. In this joint European Society of Anaesthesiology and Intensive Care (ESAIC) and British Journal of Anaesthesia (BJA) guideline on airway management in neonates and infants, we present aggregated and evidence-based recommendations to assist clinicians in providing safe and effective medical care. We identified seven main areas of interest for airway management: i) preoperative assessment and preparation; ii) medications; iii) techniques and algorithms; iv) identification and treatment of difficult airways; v) confirmation of tracheal intubation; vi) tracheal extubation, and vii) human factors. Based on these areas, Population, Intervention, Comparison, Outcomes (PICO) questions were derived that guided a structured literature search. GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methodology was used to formulate the recommendations based on those studies included with consideration of their methodological quality (strong '1' or weak '2' recommendation with high 'A', medium 'B' or low 'C' quality of evidence). In summary, we recommend: 1. Use medical history and physical examination to predict difficult airway management (1С). 2. Ensure adequate level of sedation or general anaesthesia during airway management (1B). 3. Administer neuromuscular blocker before tracheal intubation when spontaneous breathing is not necessary (1С). 4. Use a videolaryngoscope with an age-adapted standard blade as first choice for tracheal intubation (1B). 5. Apply apnoeic oxygenation during tracheal intubation in neonates (1B). 6. Consider a supraglottic airway for rescue oxygenation and ventilation when tracheal intubation fails (1B). 7. Limit the number of tracheal intubation attempts (1C). 8. Use a stylet to reinforce and preshape tracheal tubes when hyperangulated videolaryngoscope blades are used and when the larynx is anatomically anterior (1C). 9. Verify intubation is successful with clinical assessment and end-tidal CO2 waveform (1C). 10. Apply high-flow nasal oxygenation, continuous positive airway pressure or nasal intermittent positive pressure ventilation for postextubation respiratory support, when appropriate (1B)