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

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

Quantitative Imaging of Regional Aerosol Deposition, Lung Ventilation and Morphology by Synchrotron Radiation CT

To understand the determinants of inhaled aerosol particle distribution and targeting in the lung, knowledge of regional deposition, lung morphology and regional ventilation, is crucial. No single imaging modality allows the acquisition of all such data together. Here we assessed the feasibility of dual-energy synchrotron radiation imaging to this end in anesthetized rabbits; both in normal lung (n = 6) and following methacholine (MCH)-induced bronchoconstriction (n = 6), a model of asthma. We used K-edge subtraction CT (KES) imaging to quantitatively map the regional deposition of iodine-containing aerosol particles. Morphological and regional ventilation images were obtained, followed by quantitative regional iodine deposition maps, after 5 and 10 minutes of aerosol administration. Iodine deposition was markedly inhomogeneous both in normal lung and after induced bronchoconstrition. Deposition was significantly reduced in the MCH group at both time points, with a strong dependency on inspiratory flow in both conditions (R-2 = 0.71; p <0.0001). We demonstrate for the first time, the feasibility of KES CT for quantitative imaging of lung deposition of aerosol particles, regional ventilation and morphology. Since these are among the main factors determining lung aerosol deposition, we expect this imaging approach to bring new contributions to the understanding of lung aerosol delivery, targeting, and ultimately biological efficacy.Peer reviewe

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

Effects of long-term low-dose oxygen supplementation on the epithelial function, collagen metabolism and interstitial fibrogenesis in the guinea pig lung

<p>Abstract</p> <p>Background</p> <p>The patient population receiving long-term oxygen therapy has increased with the rising morbidity of COPD. Although high-dose oxygen induces pulmonary edema and interstitial fibrosis, potential lung injury caused by long-term exposure to low-dose oxygen has not been fully analyzed. This study was designed to clarify the effects of long-term low-dose oxygen inhalation on pulmonary epithelial function, edema formation, collagen metabolism, and alveolar fibrosis.</p> <p>Methods</p> <p>Guinea pigs (n = 159) were exposed to either 21% or 40% oxygen for a maximum of 16 weeks, and to 90% oxygen for a maximum of 120 hours. Clearance of inhaled technetium-labeled diethylene triamine pentaacetate (Tc-DTPA) and bronchoalveolar lavage fluid-to-serum ratio (BAL/Serum) of albumin (ALB) were used as markers of epithelial permeability. Lung wet-to-dry weight ratio (W/D) was measured to evaluate pulmonary edema, and types I and III collagenolytic activities and hydroxyproline content in the lung were analyzed as indices of collagen metabolism. Pulmonary fibrotic state was evaluated by histological quantification of fibrous tissue area stained with aniline blue.</p> <p>Results</p> <p>The clearance of Tc-DTPA was higher with 2 week exposure to 40% oxygen, while BAL/Serum Alb and W/D did not differ between the 40% and 21% groups. In the 40% oxygen group, type I collagenolytic activities at 2 and 4 weeks and type III collagenolytic activity at 2 weeks were increased. Hydroxyproline and fibrous tissue area were also increased at 2 weeks. No discernible injury was histologically observed in the 40% group, while progressive alveolar damage was observed in the 90% group.</p> <p>Conclusion</p> <p>These results indicate that epithelial function is damaged, collagen metabolism is affected, and both breakdown of collagen fibrils and fibrogenesis are transiently induced even with low-dose 40% oxygen exposure. However, these changes are successfully compensated even with continuous exposure to low-dose oxygen. We conclude that long-term low-dose oxygen exposure does not significantly induce permanent lung injury in guinea pigs.</p

Platelet-rich plasma for regeneration of neural feedback pathways around dental implants: a concise review and outlook on future possibilities

published_or_final_versio

Teaching and Learning of Calculus

This survey focuses on the main trends in the field of calculus education. Despite their variety, the findings reveal a cornerstone issue that is strongly linked to the formalism of calculus concepts and to the difficulties it generates in the learning and teaching process. As a complement to the main text, an extended bibliography with some of the most important references on this topic is included. Since the diversity of the research in the field makes it difficult to produce an exhaustive state-of-the-art summary, the authors discuss recent developments that go beyond this survey and put forward new research questions

Difficult tracheal intubation in neonates and infants. NEonate and Children audiT of Anaesthesia pRactice IN Europe (NECTARINE): a prospective European multicentre observational study

Background: Neonates and infants are susceptible to hypoxaemia in the perioperative period. The aim of this study was to analyse interventions related to anaesthesia tracheal intubations in this European cohort and identify their clinical consequences. Methods: We performed a secondary analysis of tracheal intubations of the European multicentre observational trial (NEonate and Children audiT of Anaesthesia pRactice IN Europe [NECTARINE]) in neonates and small infants with difficult tracheal intubation. The primary endpoint was the incidence of difficult intubation and the related complications. The secondary endpoints were the risk factors for severe hypoxaemia attributed to difficult airway management, and 30 and 90 day outcomes. Results: Tracheal intubation was planned in 4683 procedures. Difficult tracheal intubation, defined as two failed attempts of direct laryngoscopy, occurred in 266 children (271 procedures) with an incidence (95% confidence interval [CI]) of 5.8% (95% CI, 5.1e6.5). Bradycardia occurred in 8% of the cases with difficult intubation, whereas a significant decrease in oxygen saturation (SpO2&lt;90% for 60 s) was reported in 40%. No associated risk factors could be identified among comorbidities, surgical, or anaesthesia management. Using propensity scoring to adjust for confounders, difficult anaesthesia tracheal intubation did not lead to an increase in 30 and 90 day morbidity or mortality. Conclusions: The results of the present study demonstrate a high incidence of difficult tracheal intubation in children less than 60 weeks post-conceptual age commonly resulting in severe hypoxaemia. Reassuringly, the morbidity and mortality at 30 and 90 days was not increased by the occurrence of a difficult intubation event. Clinical trial registration: NCT02350348

Morbidity and mortality after anaesthesia in early life: results of the European prospective multicentre observational study, neonate and children audit of anaesthesia practice in Europe (NECTARINE)

BACKGROUND: Neonates and infants requiring anaesthesia are at risk of physiological instability and complications, but triggers for peri-anaesthetic interventions and associations with subsequent outcome are unknown. METHODS: This prospective, observational study 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. The primary aim was to identify thresholds of pre-determined physiological variables that triggered a medical intervention. The secondary aims were to evaluate morbidities, mortality at 30 and 90 days, or both, and associations with critical events. RESULTS: Infants (n=5609) born at mean (standard deviation [sd]) 36.2 (4.4) weeks postmenstrual age (35.7% preterm) underwent 6542 procedures within 63 (48) days of birth. Critical event(s) requiring intervention occurred in 35.2% of cases, mainly hypotension (>30% decrease in blood pressure) or reduced oxygenation (SpO2 <85%). Postmenstrual age influenced the incidence and thresholds for intervention. Risk of critical events was increased by prior neonatal medical conditions, congenital anomalies, or both (relative risk [RR]=1.16; 95% confidence interval [CI], 1.04–1.28) and in those requiring preoperative intensive support (RR=1.27; 95% CI, 1.15–1.41). Additional complications occurred in 16.3% of patients by 30 days, and overall 90-day mortality was 3.2% (95% CI, 2.7–3.7%). Co-occurrence of intraoperative hypotension, hypoxaemia, and anaemia was associated with increased risk of morbidity (RR=3.56; 95% CI, 1.64–7.71) and mortality (RR=19.80; 95% CI, 5.87–66.7). CONCLUSIONS: Variability in physiological thresholds that triggered an intervention, and the impact of poor tissue oxygenation on patient's outcome, highlight the need for more standardised perioperative management guidelines for neonates and infants