Early goal-directed hemodynamic therapy based on cardiac index, stroke volume variation, and optimized global end-diastolic volume index reduces complications and length of ICU stay after cardiac surgery.

Background A preliminary national audit of real fasting times including 3324 children showed that the fasting times for clear fluids and light meals were frequently shorter than recommended in current guidelines, but the sample size was too small for subgroup analyses. Aims Therefore, the primary aim of this extended study with more participating centers and a larger sample size was to determine whether shortened fasting times for clear fluids or light meals have an impact on the incidence of regurgitation or pulmonary aspiration during general anesthesia in children. The secondary aim was to evaluate the impact of age, emergent status, ASA classification, induction method, airway management or surgical procedure. Methods After the Ethics Committee's approval, at least more than 10 000 children in total were planned to be enrolled for this analysis. Patient demographics, real fasting times, anesthetic and surgical procedures, and occurrence of target adverse events defined as regurgitation or pulmonary aspiration were documented using a standardized case report form. Results At fifteen pediatric centers, 12 093 children scheduled for surgery or interventional procedures were included between October 2018 and December 2019. Fasting times were shorter than recommended in current guidelines for large meals in 2.5%, for light meals in 22.4%, for formula milk in 5.3%, for breastmilk in 10.9%, and for clear fluids in 39.2%. Thirty‐one cases (0.26%) of regurgitation, ten cases (0.08%) of suspected pulmonary aspiration, and four cases (0.03%) of confirmed pulmonary aspiration were reported, and all of them recovered quickly without any consequences. Fasting times for clear fluids shortened from 2 hours to 1 hour did not affect the incidence of adverse events (upper limit 95% CI 0.08%). The sample size of the cohort with fasting times for light meals shorter than 6 hours was too small for a subgroup analysis. An age between one and 3 years (odds ratio 2.7,95% CI 1.3 to 5.8%; P < .01) and emergent procedures (odds ratio 2.8,95% CI 1.4 to 5.7;P < .01) increased the incidence of adverse events, whereas ASA classification, induction method, or surgical procedure had no influence. The clear fluid fasting times were shortest under 6/4/0 as compared to 6/4/1 and 6/4/2 fasting regimens, all with an incidence of 0.3% for adverse events. Conclusion This study shows that a clear fluid fasting time shortened from 2 hours to 1 hour does not affect the incidence of regurgitation or pulmonary aspiration, that an age between one and 3 years and emergent status increase the incidence of regurgitation or pulmonary aspiration, and that pulmonary aspiration followed by postoperative respiratory distress is rare and usually shows a quick recovery.

Background Children suffering from mucopolysaccharidoses (subtypes I, II, III, IV, VI, and VII) or mucolipidoses often require anesthesia, but are at high risk for perioperative adverse events. However, the impact of the disease subtype and the standard of care for airway management are still unclear. Aims This study aimed to assess independent risk factors for perioperative adverse events in individuals with mucopolysaccharidoses/mucolipidoses and to analyze the interaction with the primary airway technique implemented. Methods This retrospective study included individuals with mucopolysaccharidoses/mucolipidoses who underwent anesthesia at two high‐volume centers from 2002 to 2016. The data were analyzed in a multivariate hierarchical model, accounting for repeated anesthesia procedures within the same patient and for multiple events within a single anesthesia. Results Of 141 identified inpatients, 67 (63 mucopolysaccharidoses and 4 mucolipidoses) underwent 269 anesthesia procedures (study cases) for 353 surgical or diagnostic interventions. At least one perioperative adverse event occurred in 25.6% of the cases. The risk for perioperative adverse events was higher in mucopolysaccharidoses type I (OR 8.0 [1.5‐42.7]; P = .014) or type II (OR 8.8 [1.3‐58.6]; P = .025) than in type III. Fiberoptic intubation through a supraglottic airway was associated with the lowest risk for perioperative adverse events and lowest conversion rate. Direct laryngoscopy was associated with a significantly higher risk for airway management problems than indirect techniques (estimated event rates 47.8% vs 10.1%, OR 24.05 [5.20‐111.24]; P < .001). The risk for respiratory adverse events was significantly higher for supraglottic airway (22.6%; OR 31.53 [2.79‐355.88]; P = .001) and direct laryngoscopy (14.8%; OR 14.70 [1.32‐163.44]; P = .029) than for fiberoptic intubation through a supraglottic airway (2.1%). Conclusions The disease subtype and primary airway technique were the most important independent risk factors for perioperative adverse events. Our findings indicate that in MPS/ML children with predicted difficult airway indirect techniques should be favored for the first tracheal intubation attempt.

Background Prolonged fasting before anesthesia is still common in children. Shortened fasting times may improve the metabolic and hemodynamic condition during induction of anesthesia and the perioperative experience for parents and children and simplify perioperative management. As a consequence, some centers in Germany have reduced fasting requirements, but the national guidelines are still unchanged. Aims This prospective multicenter observational study was initiated by the Scientific Working Group for Pediatric Anesthesia of the German Society of Anesthesiology and Intensive Care Medicine to evaluate real fasting times and the incidence of pulmonary aspiration before a possible revision of national fasting guidelines. Methods After the Ethics Committee's approval, at least 3000 children were planned to be enrolled for this analysis. Patient demographics, real fasting times, anesthetic and surgical procedures and occurrence of regurgitation or pulmonary aspiration were documented using a standardized case report form. Results were presented as median [interquartile range] (range) or incidence (percentage). Results At ten pediatric centers, 3324 children were included between October 2018 and May 2019. The real fasting times for large meals were 14 [12.2‐15.6] (0.5‐24) hours, for light meals 9 [5.6‐13.3] (0.25‐28.3) hours, for formula milk 5.8 [4.5‐7.4] (0.9‐24) hours, for breast milk 4.8 [4.2‐6.3] (1.3‐25.3) hours and for clear fluids 2.7 [1.5‐6] (0.03‐22.8) hours. Prolonged fasting (deviation from guideline >2 hours) was reported for large meals in 88.3%, for light meals in 54.7%, for formula milk in 44.4%, for breast milk in 25.8% and for clear fluids in 34.2%. Eleven cases (0.33%) of regurgitation, four cases (0.12%) of suspected pulmonary aspiration and two cases (0.06%) of confirmed pulmonary aspiration were reported; all of them could be extubated after the end of the procedure and recovered without any incidents. Conclusion This study shows that prolonged fasting is still common in pediatric anesthesia in Germany that pulmonary aspiration with postoperative respiratory distress is rare and that improvements to current local fasting regimens and national fasting guidelines are urgently needed.

The peptide hormone glucagon stimulates hepatic glucose output, and its levels in the blood are elevated in type 2 diabetes mellitus. The nuclear receptor peroxisome proliferator-activated receptor-␥ (PPAR␥) has essential roles in glucose homeostasis, and thiazolidinedione PPAR␥ agonists are clinically important antidiabetic drugs. As part of their antidiabetic effect, thiazolidinediones such as rosiglitazone have been shown to inhibit glucagon gene transcription through binding to PPAR␥ and inhibition of the transcriptional activity of PAX6 that is required for cell-specific activation of the glucagon gene. However, how thiazolidinediones and PPAR␥ inhibit PAX6 activity at the glucagon promoter remained unknown. After transient transfection of a glucagon promoter-reporter fusion gene into a glucagonproducing pancreatic islet ␣-cell line, ligand-bound PPAR␥ was found in the present study to inhibit glucagon gene transcription also after deletion of its DNA-binding domain. Like PPAR␥ ligands, also retinoid X receptor (RXR) agonists inhibited glucagon gene transcription in a PPAR␥-dependent manner. In glutathione transferase pull-down assays, the ligand-bound PPAR␥-RXR heterodimer bound to the transactivation domain of PAX6. This interaction depended on the presence of the ligand and RXR, but it was independent of the PPAR␥ DNA-binding domain. Chromatin immunoprecipitation experiments showed that PPAR␥ is recruited to the PAX6-binding proximal glucagon promoter. Taken together, the results of the present study support a model in which a ligand-bound PPAR␥-RXR heterodimer physically interacts with promoter-bound PAX6 to inhibit glucagon gene transcription. These data define PAX6 as a novel physical target of PPAR␥-RXR.Peroxisome proliferator-activated receptor-␥ (PPAR␥) belongs to the superfamily of ligand-regulated nuclear hormone receptors (Desvergne and Wahli, 1999). It can be structurally subdivided into an amino-terminal, ligand-independent transactivation domain (AF-1) followed by a DNA-binding domain and a carboxyl-terminal, ligand-binding domain that contains a second, ligand-dependent transactivation surface (AF-2) (Desvergne and Wahli, 1999). PPAR␥ binds as a heterodimer with the 9-cis-retinoic acid (9cis-RA) receptor (RXR) to response elements (PPREs) in target genes to activate transcription. Upon ligand binding and depending on the tissue-specific cofactor environment, the PPAR␥-RXR heterodimer recruits coactivators to stimulate promoter activity. This recruitment is dependent on ligand-induced allosteric alterations in the AF-2 helical domain (Nolte et al., 1998). In addition to transcriptional stimulation, PPAR␥ has been shown to be also capable of repression of gene transcription (Ricote et al., 1998;Schinner et al., 2002) PPAR␥ is thought to be involved in a broad-range of cellular functions, including adipocyte differentiation, inflammation, blood pressure regulation, and apoptosis, and in chronic This work was supported by Deutsche Forschungsgemeinschaft grant SFB402/A3, GRK335.Article, p...

all are aware a study is being conducted. This problem arises in every nonblinded study in the ICU, especially when the team feels committed toward 1 approach (the more advanced one in this study). The only method to alleviate such bias would be to directly monitor the interventions, but I'm not certain that such an approach is feasible, and even if it were that it would resolve this bias completely. Despite these reservations, this is an excellent study that shows for the first time that the content of a protocol is important.

The number of pediatric procedural sedations for diagnostic and minor therapeutic procedures performed outside the operating room has increased. Therefore, we established a specialized interdisciplinary team of pediatric anesthesiologists and intensivists (Children’s Analgosedation Team, CAST) at our tertiary-care university hospital and retrospectively analyzed the first year after implementation of the CAST. Within one year, 784 procedural sedations were performed by the CAST; 12.2% of the patients were infants <1 year, 41.9% of the patients were classified as American Society of Anesthesiologists (ASA) grade III or IV. Most children received propofol (79%) and, for painful procedures, additional esketamine (48%). Adverse events occurred in 51 patients (6.5%), with a lack of professional experience (OR 0.60; 95% CI 0.42–0.81) and increased propofol dosage (OR 1.33; 95% CI 1.17–1.55) being significant predictors. Overall, the CAST enabled safe and effective procedural sedation in children outside the operating room.

BACKGROUND: Diastolic dysfunction is a risk factor for postoperative major cardiovascular events. During anesthesia, patients with diastolic dysfunction might experience impaired hemodynamic function and worsening of diastolic function, which in turn, might be associated with a higher incidence of postoperative complications. We aimed to investigate whether patients with diastolic dysfunction require higher doses of norepinephrine during general anesthesia. Furthermore, we aimed to examine the association between the grade of diastolic dysfunction and the E/e’ ratio during anesthesia. A high E/e’ ratio corresponds to elevated filling pressures and is an important measure of impaired diastolic function. METHODS: We conducted a prospective observational cohort study at a German university hospital from February 2017 to September 2018. Patients aged ≥60 years and undergoing general anesthesia (ie, propofol and sevoflurane) for elective noncardiac surgery were enrolled. Exclusion: mitral valve disease, atrial fibrillation, and implanted mechanical device. The primary outcome parameter was the administered dose of norepinephrine within 30 minutes after anesthesia induction (μg·kg−1 30 min−1). The secondary outcome parameter was the change of Doppler echocardiographic E/e’ from ECHO1 (baseline) to ECHO2 (anesthesia). Linear models and linear mixed models were used for statistical evaluation. RESULTS: A total of 247 patients were enrolled, and 200 patients (75 female) were included in the final analysis. Diastolic dysfunction at baseline was not associated with a higher dose of norepinephrine during anesthesia (P = .6953). The grade of diastolic dysfunction at baseline was associated with a decrease of the E/e’ ratio during anesthesia (P < .001). CONCLUSIONS: We did not find evidence for an association between diastolic dysfunction and impaired hemodynamic function, as expressed by high vasopressor support during anesthesia. Additionally, our findings suggest that diastolic function, as expressed by the E/e’ ratio, does not worsen during anesthesia.