Effective ventilation and chest compressions during neonatal resuscitation - the role of the respiratory device.

BACKGROUND: The success of cardiopulmonary resuscitation (CPR) in newborns largely depends on effective lung ventilation; however, a direct randomized comparison using different available devices has not yet been performed. METHODS: Thirty-six professionals were exposed to a realistic newborn CPR scenario. Ventilation with either a bag-valve mask (BVM), T-piece, or ventilator was applied in a randomized manner during CPR using a Laerdal manikin. The primary outcome was the number of unimpaired inflations, defined as the peak of the inflation occurring after chest compression and lasting at least 0.35 s before the following chest compression takes place. The secondary outcomes were tidal volume delivered and heart compression rate. To simulate potential distractions, the entire scenario was performed with or without a quiz. Statistically, a mixed model assessing fixed effects for experience, profession, device, and distraction was used to analyze the data. For direct comparison, one-way ANOVA with Bonferroni's correction was applied. RESULTS: The number of unimpaired inflations was highest in health care professionals using the BVM with a mean ± standard deviation of 12.8 ± 2.8 (target: 15 within 30 s). However, the tidal volumes were too large in this group with a tidal volume of 42.5 ± 10.9 ml (target: 25-30 ml). The number of unimpaired breaths with the mechanical ventilator and the T-piece system were 11.6 (±3.6) and 10.1 (±3.7), respectively. Distraction did not change these outcomes, except for the significantly lower tidal volumes with the T-piece during the quiz. CONCLUSIONS: In summary, for our health care professionals, ventilation using the mechanical ventilator seemed to provide the best approach during CPR, especially in a population of preterm infants prone to volutrauma.

Case report: Intrapulmonary tidal volumes in a preterm infant with chest wall rigidity.

Background: Chest wall rigidity is a known side effect of fentanyl use, which is why fentanyl is usually combined with a muscle relaxant such as mivacurium. Verifying endotracheal intubation is difficult in case of a rigid chest wall. Case presentation: We present the case of a preterm infant (29 completed weeks gestation, birth weight 1,150 g) with a prolonged chest wall rigidity after fentanyl administration for intubation despite adequate doses of mivacurium. This resulted in a pronounced desaturation without any effect on heart rate. Clinically, the infant showed no chest wall movement despite intubation and common tools to verify intubation (including end-tidal carbon dioxide measurement and auscultation) were inconclusive. However, using electrical impedance tomography (EIT), we were able to demonstrate minimal tidal volumes at lung level and thereby, EIT was able to accurately show correct placement of the endotracheal tube. Conclusions: This case may increase vigilance for fentanyl-induced chest wall rigidity in the neonatal population even when simultaneously administering mivacurium. Higher airway pressures exceeding 30 mmHg and the use of µ-receptor antagonists such as naloxone should be considered to reverse opioid-induced chest wall rigidity. Most importantly, our data may imply a relevant clinical benefit of using EIT during neonatal intubation as it may accurately show correct endotracheal tube placement.

Endocannabinoid and steroid analysis in infant and adult nails by LC-MS/MS.

A common method to quantify chronic stress is the analysis of stress markers in keratinized matrices such as hair or nail. In this study, we aimed to validate a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the combined quantification of steroid hormones and endocannabinoids (eCBs) in the keratinized matrix nail. Furthermore, we aimed to investigate the suitability of the nail matrix for the detection of these stress markers in a pilot study. An LC-MS/MS method was used for the simultaneous identification and quantification of four eCBs (2-arachidonoylglycerol (2-AG), anandamide (AEA), oleoylethanolamide (OEA), palmitoylethanolamide (PEA)) and five steroid hormones (cortisol, cortisone, androstenedione, progesterone, testosterone) in human nails using a surrogate analyte method for each analyte. The method was validated in terms of selectivity, response factor, linearity, limit of quantification (LOQ), precision, accuracy, matrix effect, recovery, robustness, and autosampler stability. Nail samples were extracted for 1 h with methanol following a clean-up with a fully automated supported liquid extraction (SLE). The influence of nail weight on the quantification was investigated by using 0.5-20 mg of nail sample. As a proof of concept, nail samples (N = 57) were analyzed from a cohort representing newborns (1 month old), children (between 1 and 10 years), and adults (up to 43 years). It could be shown that the established workflow using a 1 hour extraction and clean-up by SLE was very robust and resulted in a short sample preparation time. The LC-MS/MS method was successfully validated. Matrix effects with ion enhancement occurred mainly for 2-AG. Sample weights below 5 mg showed variations in quantification for some analytes. Certain analytes such as PEA and progesterone could be accurately quantified at a sample weight lower than 5 mg. This is the first study where steroids and eCBs could be simultaneously detected and quantified in infant and adult nails. These results show that nails may serve as an alternative keratinized matrix (compared to hair) for the retrospective monitoring of cumulative eCB and steroid hormone levels. The combined assessment of eCBs and steroids from nails could provide a new approach to gain new insights into stress exposure in newborns and adults.

A Potential Treatment of Congenital Sodium Diarrhea in Patients With Activating GUCY2C Mutations.

INTRODUCTION: Gain-of-function mutations in guanylyl cyclase C (GCC) result in persistent diarrhea with perinatal onset. We investigated a specific GCC inhibitor, SSP2518, for its potential to treat this disorder. METHODS: We investigated the effect of SSP2518 on GCC-mediated intracellular cyclic guanosine monophosphate (cGMP) levels and on GCC-mediated chloride secretion in intestinal organoids from 3 patients with distinct activating GCC mutations and from controls, with and without stimulation of GCC with heat-stable enterotoxin. RESULTS: Patient-derived organoids had significantly higher basal cGMP levels than control organoids, which were lowered by SSP2518 to levels found in control organoids. In addition, SSP2518 significantly reduced cGMP levels and chloride secretion in patient-derived and control organoids (P < 0.05 for all comparisons) after heat-stable enterotoxin stimulation. DISCUSSION: We reported in this study that the GCC inhibitor SSP2518 normalizes cGMP levels in intestinal organoids derived from patients with GCC gain-of-function mutations and markedly reduces cystic fibrosis transmembrane conductance regulator-dependent chloride secretion, the driver of persistent diarrhea.

Citrulline, Biomarker of Enterocyte Functional Mass and Dietary Supplement. Metabolism, Transport, and Current Evidence for Clinical Use.

L-Citrulline is a non-essential but still important amino acid that is released from enterocytes. Because plasma levels are reduced in case of impaired intestinal function, it has become a biomarker to monitor intestinal integrity. Moreover, oxidative stress induces protein citrullination, and antibodies against anti-citrullinated proteins are useful to monitor rheumatoid diseases. Citrullinated histones, however, may even predict a worse outcome in cancer patients. Supplementation of citrulline is better tolerated compared to arginine and might be useful to slightly improve muscle strength or protein balance. The following article shall provide an overview of L-citrulline properties and functions, as well as the current evidence for its use as a biomarker or as a therapeutic supplement.

Newborn Incubators Do Not Protect from High Noise Levels in the Neonatal Intensive Care Unit and Are Relevant Noise Sources by Themselves.

BACKGROUND: While meaningful sound exposure has been shown to be important for newborn development, an excess of noise can delay the proper development of the auditory cortex. AIM: The aim of this study was to assess the acoustic environment of a preterm baby in an incubator on a newborn intensive care unit (NICU). METHODS: An empty but running incubator (Giraffe Omnibed, GE Healthcare) was used to evaluate the incubator frequency response with 60 measurements. In addition, a full day and night period outside and inside the incubator at the NICU of the University Hospital Zurich was acoustically analyzed. RESULTS: The fan construction inside the incubator generates noise in the frequency range of 1.3-1.5 kHz with a weighted sound pressure level (SPL) of 40.5 dB(A). The construction of the incubator narrows the transmitted frequency spectrum of sound entering the incubator to lower frequencies, but it does not attenuate transient noises such as alarms or opening and closing of cabinet doors substantially. Alarms, as generated by the monitors, the incubator, and additional devices, still pass to the newborn. CONCLUSIONS: The incubator does protect only insufficiently from noise coming from the NICUThe transmitted frequency spectrum is changed, limiting the impact of NICU noise on the neonate, but also limiting the neonate's perception of voices. The incubator, in particular its fan, as well as alarms from patient monitors are major sources of noise. Further optimizations with regard to the sound exposure in the NICU, as well as studies on the role of the incubator as a source and modulator, are needed to meet the preterm infants' multi-sensory needs.

Corrigendum: Microbial Colonization From the Fetus to Early Childhood-A Comprehensive Review.

[This corrects the article DOI: 10.3389/fcimb.2020.573735.].

Comparison between intraoperative bleeding score and ROTEM® measurements to assess coagulopathy during major pediatric surgery.

PURPOSE: Intraoperative bleeding should be regularly assessed visually to guide coagulation management. Whereas viscoelastic testing with ROTEM® measurement has been proven to be useful in detecting coagulopathies, the visual assessment is not standardized. This study therefore aims to compare a standardized visual assessment with ROTEM® results. METHODS: A 5-point bleeding score was created and applied in a recently published randomized controlled trial in major pediatric non-cardiac surgery. This score assesses overall bleeding tendency and the occurrence of diffuse bleeding, aqueous bleeding, bleeding outside the operative field, and the ability to control bleeding. Validity of this score was tested by post hoc comparison to the results of simultaneously performed ROTEM® measurements. RESULTS: Signs of coagulopathic bleeding were assessed at 183 time points. Mild to moderate bleeding intensity was judged at 103 time points, in 42 % abnormal ROTEM® traces were obtained simultaneously. When severe bleeding was scored, abnormal ROTEM values occurred in 58 %, and FIBTEM-values were significantly lower than in the "no bleeding group". Altogether, the correlation between bleeding score and ROTEM® measurements was not significant. CONCLUSIONS: The standardized visual assessment did not correlate well with ROTEM® measurements, suggesting that it is not useful to detect coagulopathy. Trial registry number: ClinicalTrials.gov identifier No. NCT01487837.

New Parents Experienced Lower Parenting Self-Efficacy during the COVID-19 Pandemic Lockdown.

Background: The COVID-19 pandemic is a global issue which affects the entire population's mental health. This study evaluates how restrictions to curtail this pandemic change parenting self-efficacy, depressive symptoms, couple satisfaction and health-related quality of life in parents after delivery of a newborn. Methods: In this prospective single center evaluation of parental self-efficacy and quality of life, four validated questionnaires were used to repeatedly assess parenting self-efficacy (Tool to measure Parental Self-Efficacy, TOPSE), depressive symptoms (Edinburgh Postnatal Depression Scale, EPDS), couple satisfaction (Couple Satisfaction Index, CSI) and health-related quality of life (short form 12, SF12). Fifty-three parents of 50 infants answered a total number of 63 questionnaires during the lockdown period to limit the spread of COVID-19. These questionnaires were matched with 63 questionnaires of 58 other parents that had answered them before or after strong pandemic related measures. Results: Parents experienced lower parenting self-efficacy during the strict pandemic measures as compared to before and after (p = 0.04). In terms of age, socioeconomic, marital status and duration of hospitalization we detected no significant difference between both groups. On univariate linear regression, TOPSE scores were associated with gestational age (p = 0.044, parameter estimate 1.67, 95% CI: 0.048 to 3.301), birth weight (p = 0.035, parameter estimate 0.008, 95% CI: 0.001 to 0.015), number of newborns' siblings (p = 0.0554, parameter estimate 7.49, 95% CI: -0.174 to 15.145) and distance of home from hospital (p = 0.043, parameter estimate -0.38, 95% CI: -0.745 to -0.011). Interestingly, there was a positive correlation between quality of life and TOPSE scores, suggesting that those who experience a higher self-efficacy also have a higher quality of life. Conclusions: When implementing a lock-down period psychological effects such as lower experience of parental self-efficacy have to be considered.

Plasma citrulline correlates with basolateral amino acid transporter LAT4 expression in human small intestine.

BACKGROUND & AIMS: Plasma citrulline, a non-protein amino acid, is a biochemical marker of small intestine enterocyte mass in humans. Indeed, citrulline is highly correlated with residual bowel length in patients with short bowel syndrome. It is known to be synthesised in epithelial cells of the small intestine from other amino acids (precursors). Citrulline is then released into systemic circulation and interconverted into arginine in kidneys. If plasma citrulline concentration depends on abundance of intestinal amino acid transporters is not known. The aim of the present study was to explore whether plasma citrulline concentration correlates with the expression of intestinal amino acid transporters. Furthermore, we assessed if arginine in urine correlates with plasma citrulline. METHODS: Duodenal samples, blood plasma and urine were collected from 43 subjects undergoing routine gastroduodenoscopy. mRNA expression of seven basolateral membrane amino acid transporters/transporter subunits were assessed by real-time PCR. Plasma and urine amino acid concentrations of citrulline, its precursors and other amino acids were analysed using High Performance Liquid Chromatography measurements. Amino acid transporter mRNA expression was correlated with blood plasma and urine levels of citrulline and its precursors using Spearman's rank correlation. Likewise, urine arginine was correlated with plasma citrulline. RESULTS: Plasma citrulline correlated with the mRNA expression of basolateral amino acid transporter LAT4 (Spearman's r = 0.467, p = 0.028) in small intestine. None of the other basolateral membrane transporters/transporter subunits assessed correlated with plasma citrulline. Plasma citrulline correlated with urinary arginine, (Spearman's r = 0.419, p = 0.017), but not with urinary citrulline or other proteinogenic amino acids in the urine. CONCLUSIONS: In this study, we showed for the first time that small intestinal basolateral LAT4 expression correlates with plasma citrulline concentration. This finding indicates that LAT4 has an important function in mediating citrulline efflux from enterocytes. Furthermore, urine arginine correlated with plasma citrulline, indicating arginine in the urine as possible additional marker for small intestine enterocyte mass. Finally, basolateral LAT4 expression along the human small intestine was shown for the first time.

The Role of Methemoglobin and Carboxyhemoglobin in COVID-19: A Review.

Following the outbreak of a novel coronavirus (SARS-CoV-2) associated with pneumonia in China (Corona Virus Disease 2019, COVID-19) at the end of 2019, the world is currently facing a global pandemic of infections with SARS-CoV-2 and cases of COVID-19. Since severely ill patients often show elevated methemoglobin (MetHb) and carboxyhemoglobin (COHb) concentrations in their blood as a marker of disease severity, we aimed to summarize the currently available published study results (case reports and cross-sectional studies) on MetHb and COHb concentrations in the blood of COVID-19 patients. To this end, a systematic literature research was performed. For the case of MetHb, seven publications were identified (five case reports and two cross-sectional studies), and for the case of COHb, three studies were found (two cross-sectional studies and one case report). The findings reported in the publications show that an increase in MetHb and COHb can happen in COVID-19 patients, especially in critically ill ones, and that MetHb and COHb can increase to dangerously high levels during the course of the disease in some patients. The medications given to the patient and the patient's glucose-6-phospate dehydrogenase (G6PD) status seem to be important factors determining the severity of the methemoglobinemia and carboxyhemoglobinemia. Therefore, G6PD status should be determined before medications such as hydroxychloroquine are administered. In conclusion, MetHb and COHb can be elevated in COVID-19 patients and should be checked routinely in order to provide adequate medical treatment as well as to avoid misinterpretation of fingertip pulse oximetry readings, which can be inaccurate and unreliable in case of elevated MetHb and COHb levels in the blood.

Microbial Colonization From the Fetus to Early Childhood-A Comprehensive Review.

The development of the neonatal gastrointestinal tract microbiota remains a poorly understood process. The interplay between neonatal (gestational age, genetic background), maternal (mode of delivery, nutritional status) and environmental factors (antibiotic exposure, available nutrition) are thought to influence microbial colonization, however, the exact mechanisms are unclear. Derangements in this process likely contribute to various gastrointestinal diseases including necrotizing enterocolitis and inflammatory bowel disease. As such, enhanced understanding of microbiota development may hold the key to significantly reduce the burden of gastrointestinal disease in the pediatric population. The most debatable topics during microbial seeding and possible future treatment approaches will be highlighted in this review.

Limited Neonatal Carbohydrate-Specific Antibody Repertoire Consecutive to Partial Prenatal Transfer of Maternal Antibodies.

Despite the prominence of carbohydrate-specific antibodies in human sera, data on their emergence and antigen specificities are limited. Whereas maternal IgG are transferred prenatally to the fetal circulation, IgM present in cord blood originate from fetal B lymphocytes. Considering the limited exposure of the fetus to foreign antigens, we assessed the repertoire of carbohydrate-specific antibodies in human cord blood and matched maternal blood samples using glycan arrays. Carbohydrate-specific IgM was absent in cord blood, whereas low cord blood IgG reactivity to glycans was detectable. Comparing IgG reactivities of matched pairs, we observed a general lack of correlation in the antigen specificity of IgG from cord blood and maternal blood due to a selective exclusion of most carbohydrate-specific IgG from maternofetal transfer. Given the importance of intestinal bacteria in inducing carbohydrate-specific antibodies, we analyzed global antibody specificities toward commensal bacteria. Similar IgG reactivities to specific Bacteroides species were detected in matched cord and maternal blood samples, thus pointing to an efficient maternal transfer of anti-microbial IgG. Due to the observed selectivity in maternofetal IgG transfer, the lack of fetal antibodies to carbohydrate epitopes is only partially compensated by maternal IgG, thus resulting in a weak response to carbohydrate antigens in neonates.

Sevoflurane sedation attenuates early cerebral oedema formation through stabilisation of the adherens junction protein beta catenin in a model of subarachnoid haemorrhage: A randomised animal study.

BACKGROUND: Severe neurological impairment is a problem after subarachnoid haemorrhage (SAH). Although volatile anaesthetics, such as sevoflurane, have demonstrated protective properties in many organs, their use in cerebral injury is controversial. Cerebral vasodilation may lead to increased intracranial pressure (ICP), but at the same time volatile anaesthetics are known to stabilise the SAH-injured endothelial barrier. OBJECTIVE: To test the effect of sevoflurane on ICP and blood-brain barrier function. DESIGN: Randomised study. PARTICIPANTS: One hundred male Wistar rats included, 96 analysed. INTERVENTIONS: SAH was induced by the endoluminal filament method under ketamine/xylazine anaesthesia. Fifteen minutes after sham surgery or induction of SAH, adult male Wistar rats were randomised to 4 h sedation with either propofol or sevoflurane. MAIN OUTCOME MEASURES: Mean arterial pressure (MAP), ICP, extravasation of water (small), Evan's blue (intermediate) and IgG (large molecule) were measured. Zonula occludens-1 (ZO-1) and beta-catenin (ß-catenin), as important representatives of tight and adherens junction proteins, were determined by western blot. RESULTS: Propofol and sevoflurane sedation did not affect MAP or ICP in SAH animals. Extravasation of small molecules was higher in SAH-propofol compared with SAH-sevoflurane animals (79.1 ±â€Š0.9 vs. 78.0 ±â€Š0.7%, P = 0.04). For intermediate and large molecules, no difference was detected (P = 0.6 and P = 0.2). Both membrane and cytosolic fractions of ZO-1 as well as membrane ß-catenin remained unaffected by the injury and type of sedation. Decreased cytosolic fraction of ß-catenin in propofol-SAH animals (59 ±â€Š15%) was found to reach values of sham animals (100%) in the presence of sevoflurane in SAH animals (89 ±â€Š21%; P = 0.04). CONCLUSION: This experiment demonstrates that low-dose short-term sevoflurane sedation after SAH in vivo did not affect ICP and MAP and at the same time may attenuate early brain oedema formation, potentially by preserving adherens junctions. TRIAL REGISTRATION: No 115/2014 Veterinäramt Zürich.

An introduction to the pathophysiology of aneurysmal subarachnoid hemorrhage.

Pathophysiological processes following subarachnoid hemorrhage (SAH) present survivors of the initial bleeding with a high risk of morbidity and mortality during the course of the disease. As angiographic vasospasm is strongly associated with delayed cerebral ischemia (DCI) and clinical outcome, clinical trials in the last few decades focused on prevention of these angiographic spasms. Despite all efforts, no new pharmacological agents have shown to improve patient outcome. As such, it has become clear that our understanding of the pathophysiology of SAH is incomplete and we need to reevaluate our concepts on the complex pathophysiological process following SAH. Angiographic vasospasm is probably important. However, a unifying theory for the pathophysiological changes following SAH has yet not been described. Some of these changes may be causally connected or present themselves as an epiphenomenon of an associated process. A causal connection between DCI and early brain injury (EBI) would mean that future therapies should address EBI more specifically. If the mechanisms following SAH display no causal pathophysiological connection but are rather evoked by the subarachnoid blood and its degradation production, multiple treatment strategies addressing the different pathophysiological mechanisms are required. The discrepancy between experimental and clinical SAH could be one reason for unsuccessful translational results.

Sevoflurane protects rat brain endothelial barrier structure and function after hypoxia-reoxygenation injury.

BACKGROUND: After cerebral injury blood-brain barrier disruption significantly impairs brain homeostasis. Volatile anesthetics have been shown to be protective in ischemia-reperfusion injury scenarios. Their impact on brain endothelial cells after hypoxia-reoxygenation (H/R) has not yet been studied in detail. METHODS: Rat brain endothelial cells (RBE4) were exposed to severe hypoxia and reoxygenated in air in the presence or absence of sevoflurane. Changes in dextran permeability and architecture of the cellular junctional proteins ZO-1 and ß-catenin were measured. To determine necrosis and apoptosis rate DNA content, LDH release and caspase activity were quantified. The role of vascular endothelial growth factor (VEGF) as an inflammatory mediator increasing vascular permeability was assessed. At the same time, it was evaluated if sevoflurane effects are mediated through VEGF. Results were analyzed by unpaired t-tests or one way-analysis of variance followed by Bonferroni's correction. RESULTS: H/R led to a 172% increase in permeability (p<0.001), cell swelling and qualitatively but not quantitatively modified expression of ZO-1, ß-catenin and F-actin. In the presence of sevoflurane during reoxygenation, barrier function improved by 96% (p = 0.042) in parallel to a decrease of the cell size and less re-arranged junction proteins and F-actin. Sevoflurane-induced improvement of the barrier function could not be explained on the level of necrosis or apoptosis as they remained unchanged independent of the presence or absence of the volatile anesthetic. Increased expression of VEGF after H/R was attenuated by sevoflurane by 34% (p = 0.004). Barrier protection provided by sevoflurane was similar to the application of a blocking VEGF-antibody. Furthermore, the protective effect of sevoflurane was abolished in the presence of recombinant VEGF. CONCLUSIONS: In H/R-induced rat brain endothelial cell injury sevoflurane maintains endothelial barrier function through downregulation of VEGF, which is a key player not only in mediating injury, but also with regard to the protective effect of sevoflurane.

Sevoflurane attenuates systemic inflammation compared with propofol, but does not modulate neuro-inflammation: A laboratory rat study.

BACKGROUND: Septic encephalopathy is believed to be a result of neuro-inflammation possibly triggered by endotoxins, such as lipopolysaccharides (LPS). Modulation of the immune system is a property of volatile anaesthetics. OBJECTIVE: We aimed to investigate the systemic and cerebral inflammatory response in a LPS-induced sepsis model in rats. We compared two different sedation strategies, intravenous propofol and the volatile anaesthetic sevoflurane, with the hypothesis that the latter may attenuate neuro-inflammatory processes. DESIGN: Laboratory rat study. SETTING: Basic research laboratories at the University Hospital Zurich and University Zurich Irchel between August 2014 and June 2016. PATIENTS: A total of 32 adult male Wistar rats. INTERVENTIONS: After tracheotomy and mechanical ventilation, the anaesthetised rats were monitored before sepsis was induced by using intravenous LPS or phosphate-buffered saline as control. Rats were sedated with propofol (10 mg kg h) or sevoflurane (2 vol%) continuously for 12 h. MAIN OUTCOME MEASURES: Systemic inflammatory markers such as cytokine-induced neutrophil chemo-attractant protein 1, monocyte chemo-tactic protein-1 and IL-6 were determined. The same cytokines were measured in brain tissue. Cellular response in the brain was assessed by defining neutrophil accumulation with myeloperoxidase and also activation of microglia with ionised calcium-binding adaptor molecule-1 and astrocytes with glial fibrillary acidic protein. Finally, brain injury was determined. RESULTS: Animals were haemodynamically stable in both sedation groups treated with LPS. Blood cytokine peak values were lower in the sevoflurane-LPS compared with propofol-LPS animals. In brain tissue of LPS animals, chemoattractant protein-1 was the only significantly increased cytokine (P = 0.003), however with no significance between propofol and sevoflurane. After LPS challenge, cerebral accumulation of neutrophils was observed. Microglia activation was pronounced in the hippocampus of animals treated with LPS (P = 0.006). LPS induced prominent astrogliosis (P < 0.001). There was no significant difference in microglia or astrocyte activation or apoptosis in the brain between sevoflurane and propofol. CONCLUSION: We have shown that systemic attenuation of inflammation by the volatile anaesthetic sevoflurane did not translate into attenuated neuro-inflammation in this LPS-induced inflammation model. TRIAL REGISTRATION: Animal approval No. 134/2014, Veterinäramt Zürich.

Blind Intubation through Self-pressurized, Disposable Supraglottic Airway Laryngeal Intubation Masks: An International, Multicenter, Prospective Cohort Study.

BACKGROUND: Supraglottic airway devices commonly are used for securing the airway during general anesthesia. Occasionally, intubation with an endotracheal tube through a supraglottic airway is indicated. Reported success rates for blind intubation range from 15 to 97%. The authors thus investigated as their primary outcome the fraction of patients who could be intubated blindly with an Air-Qsp supraglottic airway device (Mercury Medical, USA). Second, the authors investigated the influence of muscle relaxation on air leakage pressure, predictors for failed blind intubation, and associated complications of using the supraglottic airway device. METHODS: The authors enrolled 1,000 adults having elective surgery with endotracheal intubation. After routine induction of general anesthesia, a supraglottic airway device was inserted and patients were ventilated intermittently. Air leak pressure was measured before and after full muscle relaxation. Up to two blind intubation attempts were performed. RESULTS: The supraglottic airway provided adequate ventilation and oxygenation in 99% of cases. Blind intubation succeeded in 78% of all patients (95% CI, 75 to 81%). However, the success rate was inconsistent among the three centers (P < 0.001): 80% (95% CI, 75 to 85%) at the Institute of Anesthesia and Pain Therapy, Kantonsspital Winterthur, Winterthur, Switzerland; 41% (95% CI, 29 to 53%) at the Department of Anesthesiology and Intensive Therapy, Medical University of Lodz, Lodz, Poland; and 84% (95% CI, 80 to 88%) at the Institute of Anesthesiology, University Hospital Zurich, Zurich, Switzerland. Leak pressure before relaxation correlated reasonably well with air leak pressure after relaxation. CONCLUSIONS: The supraglottic airway device reliably provided a good airway and allowed blind intubation in nearly 80% of patients. It is thus a reasonable initial approach to airway control. Muscle relaxation can be used safely when unparalyzed leak pressure is adequate.

A Systematic and Meta-Analysis of Mortality in Experimental Mouse Models Analyzing Delayed Cerebral Ischemia After Subarachnoid Hemorrhage.

Animal models are established to display the pathophysiological changes following subarachnoid hemorrhage (SAH). The aim of the present study was to determine case fatality in mouse delayed cerebral ischemia (DCI) models, to compare mortality in mouse DCI models to case fatality in human SAH patients, and to identify factors influencing mouse mortality. A systematic search of the PubMed database was performed to identify all studies that assessed mouse DCI models. Mortality rates and predictor variables were extracted and compared to the human case fatality after SAH as previously reported. Predictors for mouse mortality were identified through multivariate analysis. Forty-eight studies were included in the quantitative analysis. The mean overall mortality rate was 21% in mouse DCI models. However, the time period between induction of SAH and evaluation of mortality rates is a significant variable influencing the mortality rate in mouse SAH models. The experimental SAH model was the only significant predictor for mouse mortality after 48 h. In contrast, neither the genetic background nor the anesthetic changed the case fatality rate. Mouse mortality at 24, 48, and 72 h after experimental SAH in DCI models was significantly lower than human case fatality following aneurysmal SAH. The mean overall mortality rate in mouse DCI models is significantly lower than human case fatality following aneurysmal SAH. However, time between SAH induction and evaluation is a significant variable influencing the mortality rate in mouse SAH models. Further analyses will be required to establish whether and to which extent different DCI models affect mortality and reflect human pathophysiology.

Economic aspects of intraoperative coagulation management targeting higher fibrinogen concentrations during major craniosynostosis surgery.

BACKGROUND: Results of a previously published study demonstrated a significant decrease in transfusion requirements and calculated blood loss for pediatric major craniosynostosis surgery, if a ROTEM(®) FIBTEM trigger of <13 mm (early substitution group) was applied as compared to a trigger of <8 mm (conventional group). The aim of this study was a posthoc analysis of the costs for this coagulation management. METHODS: The total volume as well as the number of units or bags for all transfused blood products and coagulation factors were recorded for each case. The number of laboratory and point-of-care coagulation tests was also analyzed. Total blood product costs were calculated according to the local prices per unit. RESULTS: The total cost for all transfused/administered blood products/coagulation factors per patient was a median of 1023EUR (IQR 850EUR-1058EUR) in the early substitution group as compared to a median of 910EUR (IQR 719EUR-1351EUR) in the conventional group (P = 0.81). No difference in the number of coagulation tests performed was observed. CONCLUSION: In this study, the use of a higher fibrinogen trigger was not linked to a significant increase in total costs for transfused blood products and coagulation factors, and may offer an economically equivalent approach to coagulation management.