Quantification of muscle tone by using shear wave velocity during an anaesthetic induction: a prospective observational study.

OBJECTIVES: The quantitative assessment of muscle stiffness or weakness is essential for medical care. Shear wave elastography is non-invasive ultrasound method and provides quantitative information on the elasticity of soft tissue. However, the universal velocity scale for quantification has not been developed. The aim of the study is to determine the shear wave velocities of abdominal muscle during anesthetic induction and to identify methods to cancel the effects of confounders for future development in the quantitative assessment of muscle tone using the universal scale. METHODS: We enrolled 75 adult patients undergoing elective surgery with ASA-PS I - III in the period between December 2018 and March 2021. We measured and calculated the shear wave velocity (SWV) before and after opioid administration (i.e., the baseline at rest and opioid-induced rigidity condition), and after muscle relaxant administration (i.e., zero reference condition). The SWV value was adjusted for the subcutaneous fat thickness by our proposed corrections. The SWVs after the adjustment were compared among the values in baseline, rigidity, and relaxation using one-way repeated-measures ANOVA and post hoc Tukey-Kramer test. A p-value of < 0.05 was considered to be statistically significant. UMIN Clinical Trials Registry identifier UMIN000034692, registered on October 30, 2018. RESULTS: The SWVs in the baseline, opioid-induced rigidity, and muscle relaxation conditions after the adjustment were 2.08 ± 0.48, 2.41 ± 0.60, and 1.79 ± 0.30 m/s, respectively (p < 0.001 at all comparisons). CONCLUSION: The present study suggested that the SWV as reference was 1.79 m/s and that the SWVs at rest and opioid-induced rigidity were ~ 10% and ~ 30% increase from the reference, respectively. The SWV adjusted for the subcutaneous fat thickness may be scale points for the assessment of muscle tone.

Association between the Depth of Sevoflurane or Propofol Anesthesia and the Incidence of Emergence Agitation in Children: A Single-Center Retrospective Study.

In the present study, we investigated the hypothesis that the depth of general anesthesia affects emergence agitation (EA) in children in the early postanesthetic period. We retrospectively examined male and female children (aged 1-9 years) who underwent ambulatory surgery that lasted < 2 h. Various parameters, including the modified Yale Preoperative Anxiety Score (mYPAS) before anesthesia induction, the Pediatric Anesthesia Emergence Delirium (PAED) score at recovery time, and the value of the patient state index (PSI), were extracted from our electronic anesthesia database. The relationships between the PAED score and the mean PSI values were examined with univariate analyses. We also investigated the associations among the mean PSI, propofol anesthesia, age, mYPAS, the type of surgery, and the total amount of fentanyl divided by body weight with the PAED score using multiple regression analysis with interaction terms. There were 32 and 34 patients in the sevoflurane and propofol groups, respectively. The PAED scores (all patients: r = -0.34, p = 0.0048; sevoflurane group: r = -0.37, p = 0.036) were negatively correlated with the mean PSI, whereas the PAED score in the propofol group [r = 0.31 (-0.03, 0.59), p = 0.073] did not show a significant positive correlation with the mean PSI in the univariate analysis. The multiple linear regression analysis outcomes revealed that the mean PSI value was an independent clinical factor associated with the PAED score. Intraoperative electroencephalogram monitoring may be proved as one of the useful tools for the assessment of EA risks in children.

Chronic allergic lung inflammation negatively influences neurobehavioral outcomes in mice.

BACKGROUND: Asthma is a major public health problem worldwide. Emerging data from epidemiological studies show that allergies and allergic diseases may be linked to anxiety, depression and cognitive decline. However, little is known about the effect of asthma, an allergic lung inflammation, on cognitive decline/behavioral changes. Therefore, we investigated the hypothesis that allergic lung inflammation causes inflammation in the brain and leads to neurobehavioral changes in mice. METHODS: Wild-type C57BL/6J female mice were sensitized with nasal house dust mite (HDM) antigen or control PBS for 6 weeks to induce chronic allergic lung inflammation. A series of neurocognitive tests for anxiety and/or depression were performed before and after the intranasal HDM administration. After the behavior tests, tissues were harvested to measure inflammation in the lungs and the brains. RESULTS: HDM-treated mice exhibited significantly increased immobility times during tail suspension tests and significantly decreased sucrose preference compared with PBS controls, suggesting a more depressed and anhedonia phenotype. Spatial memory impairment was also observed in HDM-treated mice when assessed by the Y-maze novel arm tests. Development of lung inflammation after 6 weeks of HDM administration was confirmed by histology, bronchoalveolar lavage (BAL) cell count and lung cytokine measurements. Serum pro-inflammatory cytokines and Th2-related cytokines levels were elevated in HDM-sensitized mice. In the brain, the chemokine fractalkine was increased in the HDM group. The c-Fos protein, a marker for neuronal activity, Glial Fibrillary Acidic Protein (GFAP) and chymase, a serine protease from mast cells, were increased in the brains from mice in HDM group. Chymase expression in the brain was negatively correlated with the results of sucrose preference rate in individual mice. CONCLUSIONS: 6 weeks of intranasal HDM administration in mice to mimic the chronic status of lung inflammation in asthma, caused significant inflammatory histological changes in the lungs, and several behavioral changes consistent with depression and altered spatial memory. Chymase and c-Fos proteins were increased in the brain from HDM-treated mice, suggesting links between lung inflammation and brain mast cell activation, which could be responsible for depression-like behavior.

Effects of oxytocin on responses to nociceptive and non-nociceptive stimulation in the upper central nervous system.

Oxytocin is known as a social bonding hormone, but it also functions as an anxiolytic or analgesic neurotransmitter. When oxytocin regulates pain or anxiousness centrally as a neurotransmitter, it is secreted by neurons and directly projected to targeted regions. Although the function of oxytocin at the spinal level is well studied, its effects at the supraspinal level are poorly understood. We aimed to investigate the effect of oxytocin at the supraspinal level in vivo using C57BL/6J (wild-type [WT]), oxytocin-deficient (Oxt-/-), oxytocin receptor-deficient (Oxtr-/-), and oxytocin receptor-Venus (OxtrVenus/+) mice lines. Response thresholds in Oxtr-/- mice in Hargreaves and von-Frey tests were significantly lower than those in WT mice, whereas open field and light/dark tests showed no significant differences. Moreover, response thresholds in Oxt-/- mice were raised to those in WT mice after oxytocin administration. Following the Hargreaves test, we observed the co-localisation of c-fos with Venus or the oxytocin receptor in the periaqueductal gray (PAG), medial amygdala (MeA), and nucleus accumbens (NAc) regions in OxtrVenus/+ mice. Furthermore, in the PAG, MeA, and NAc regions, the co-localisation of oxytocin with c-fos and gamma-aminobutyric acid was much stronger in Oxtr-/- mice than in WT mice. However, following von-Frey test, the same findings were observed only in the MeA and NAc regions. Our results suggest that oxytocin exerts its analgesic effect on painful stimulation via the PAG region and a self-protective effect on unpleasant stimulation via the MeA and NAc regions.

Impact of clinical factors and UGT1A9 and CYP2B6 genotype on inter-individual differences in propofol pharmacokinetics.

PURPOSE: Propofol is one of the most widely used fast-acting intravenously administered anesthetics. However, although large inter-individual differences in dose requirements and recovery time have been observed, there are few previous studies in which the association between several potential covariates, including genetic factors such as the UGT1A9 and CYP2B6 genotypes, and propofol pharmacokinetics was simultaneously examined. This study aimed to identify factors determining propofol pharmacokinetics. METHODS: Eighty-three patients were enrolled, and their blood samples were collected 1, 5, 10, and 15 min after administering a single intravenous bolus of propofol at a dose of 2.0 ml/kg to measure propofol plasma concentration. Area under the time-plasma concentration curve from zero up to the last measurable time point (AUC15min) was determined from the concentration data. The inter-individual variability of the propofol pharmacokinetics was evaluated by investigating relationships between AUC15min and genotype of UGT1A9 and CYP2B6; clinical factors, such as age, sex, body mass index (BMI), and preoperative hematological examination; and hemodynamic variables measured by a pulse dye densitogram analyzer. The Spearman rank correlation coefficient and the Mann-Whitney U test were used for the statistical analysis of continuous and categorical values, respectively. Subsequently, clinical factors that had p values of < 0.05 in the univariate analysis were examined in a multivariate analysis using multiple linear regression analysis. RESULTS: Age, BMI, indocyanine green disappearance ratio (K-ICG), hepatic blood flow (HBF), preoperative hemoglobin level, and sex were correlated with AUC15min (p < 0.05) in univariate analysis. Multivariate analysis performed to adjust for age, BMI, K-ICG, HBF, preoperative hemoglobin level, and sex revealed only BMI as an independent factor associated with AUC15min. CONCLUSIONS: This study demonstrated that BMI influences propofol pharmacokinetics after its administration as a single intravenous injection, while UGT1A9 and CYP2B6 SNPs, other clinical factors, and hemodynamic variables do not. These results suggest that BMI is an independent factor associated with propofol pharmacokinetics in several potential covariates. CLINICAL TRIALS REGISTRATION NUMBER: University Hospital Medical Information Network (UMIN000022948).

Double-stranded RNA-binding protein DRB3 negatively regulates anthocyanin biosynthesis by modulating PAP1 expression in Arabidopsis thaliana.

The model plant Arabidopsis thaliana has five double-stranded RNA-binding proteins (DRB1-DRB5), two of which, DRB1 and DRB4, are well characterized. In contrast, the functions of DRB2, DRB3 and DRB5 have yet to be elucidated. In this study, we tried to uncover their functions using drb mutants and DRB-over-expressed lines. In over-expressed lines of all five DRB genes, the over-expression of DRB2 or DRB3 (DRB2ox or DRB3ox) conferred a downward-curled leaf phenotype, but the expression profiles of ten small RNAs were similar to that of the wild-type (WT) plant. Phenotypes were examined in response to abiotic stresses. Both DRB2ox and DRB3ox plants exhibited salt-tolerance. When these plants were exposed to cold stress, drb2 and drb3 over-accumulated anthocyanin but DRB2ox and DRB3ox did not. Therefore, the over-expression of DRB2 or DRB3 had pleiotropic effects on host plants. Microarray and deep-sequencing analyses indicated that several genes encoding key enzymes for anthocyanin biosynthesis, including chalcone synthase (CHS), dihydroflavonol reductase (DFR) and anthocyanidin synthase (ANS), were down-regulated in DRB3ox plants. When DRB3ox was crossed with the pap1-D line, which is an activation-tagged transgenic line that over-expresses the key transcription factor PAP1 (Production of anthocyanin pigmentation1) for anthocyanin biosynthesis, over-expression of DRB3 suppressed the expression of PAP1, CHS, DFR and ANS genes. DRB3 negatively regulates anthocyanin biosynthesis by modulating the level of PAP1 transcript. Since two different small RNAs regulate PAP1 gene expression, a possible function of DRB3 for small RNA biogenesis is discussed.

Factors affecting extubation time following pediatric ambulatory surgery: an analysis using electronic anesthesia records from an academic university hospital.

BACKGROUND: In pediatric general anesthesia, our goal should be quicker extubation to facilitate rapid turnover in the operating room without compromising on safety and quality of anesthesia. Although many studies have focused on improving safety and pursuing a higher quality of recovery, factors related to anesthesia emergence remain unclear. We must, therefore, identify factors that influence the process of emergence from general anesthesia in children. FINDINGS: We retrospectively examined 148 children (aged 1-6 years, American Society of Anesthesiologists physical status: 1-2) who had undergone <2 h of ambulatory surgery. Clinical measures included time from the end of surgery to extubation (extubation time), age, height, weight, surgical time, mean indirect blood pressure during surgery, mean heart rate during surgery, mean end-tidal carbon dioxide during surgery (mETCO2), mean body temperature during surgery (mBT), and total amount of fentanyl. Anesthetic procedures involved sevoflurane or propofol. Multiple regression analysis revealed that mETCO2 (p < 0.01) and mBT (p < 0.01) were independent clinical factors associated with extubation time following pediatric ambulatory surgery. CONCLUSIONS: This study of 148 pediatric patients demonstrated that anesthesia emergence may be associated with mBT and mETCO2 following pediatric ambulatory surgery. These results show that perioperative vital signs are important in the prevention of delayed emergence for pediatric patients.

Emergence agitation in children: risk factors, prevention, and treatment.

Emergence agitation (EA) in children is a major postoperative issue that increases the risk of patient self-harm, places a burden on nursing staff, and reduces parent satisfaction with treatment. Risk factors for EA include age, preoperative anxiety, patient personality, pain, anesthesia method, and surgical procedure. Sevoflurane and desflurane are widely used anesthetics due to their low blood/gas partition coefficients, but they have recently been posited as a cause of EA in children. The perioperative administration of opioids, midazolam, ketamine, alpha-2 agonist sedatives, and nonsteroidal anti-inflammatory drugs has demonstrated efficacy in the prevention and treatment of EA. Maintenance of anesthesia using propofol has also been shown to prevent EA. In children, anesthesia methods that are unlikely to cause EA should be selected, with the prompt adminstration of appropriate treatment in cases of EA.

Lower incidence of emergence agitation in children after propofol anesthesia compared with sevoflurane: a meta-analysis of randomized controlled trials.

BACKGROUND: Emergence agitation (EA) from general anesthesia has been reported as an adverse effect of sevoflurane in children. We describe a meta-analysis of randomized controlled trials that compared the incidence of EA between children who underwent sevoflurane anesthesia and those who underwent propofol anesthesia. METHODS: A literature search was conducted to identify clinical trials that met our inclusion criteria. Prospective randomized trials comparing sevoflurane and propofol anesthesia in children less than 15 years of age were included in the meta-analysis. Data from each trial were combined using the random effects model to calculate pooled odds ratios (ORs) and their corresponding 95 % confidence intervals (CIs). The heterogeneity of data was assessed by Cochran's Q and I (2) tests. Sensitivity analysis was conducted for study quality, patient age, and type of surgical procedure. RESULTS: The meta-analysis included 14 studies, in which 560 patients received sevoflurane and 548 received propofol. The pooled OR for EA was 0.25 with a 95 % CI of 0.16-0.39 (P = 0.000), which indicates that propofol anesthesia resulted in a lower incidence of EA. The heterogeneity of data was not statistically supported (P = 0.191). All sensitivity analyses strengthened the evidence for the lower incidence of EA with propofol. CONCLUSIONS: Our meta-analysis demonstrated that EA in children is less likely to occur after propofol anesthesia compared with sevoflurane anesthesia.

Higher fraction of inspired oxygen in anesthesia induction does not affect functional residual capacity reduction after intubation: a comparative study of higher and lower oxygen concentration.

BACKGROUND: Low fraction of inspired oxygen (FIO2) reduces the atelectasis area during anesthesia induction. However, atelectasis may occur during laryngoscopy and endotracheal intubation because lungs can collapse within a fraction of a second. We assessed the effects of ventilation with 100 and 40 % oxygen on functional residual capacity (FRC) in patients undergoing general anesthesia. METHODS: Twenty patients scheduled for elective open abdominal surgery were randomized into 40 % oxygen (GI, n = 10) and 100 % oxygen (GII, n = 10) groups and FRC was measured. Preoxygenation and mask ventilation with 40 and 100 % oxygen were used in GI and GII, respectively. In both groups, 40 % oxygen was used for anesthesia maintenance after intubation. Bilateral lung ventilation was performed with volume guarantee and low tidal volume (7 ml/kg predicted body weight) using bilevel airway pressure. We measured FRC and blood gas in all patients during preoxygenation, after intubation, and during surgery. RESULTS: FRC decreased from during preoxygenation (GI 2380 ml, GII 2313 ml) to after intubation (GI 1569 ml, GII 1586 ml) and significantly decreased during surgery (GI 1338 ml, GII 1417 ml) (P < 0.05). PaO2/FIO2 decreased from during preoxygenation (GI 419 mmHg, GII 427 mmHg) to after intubation (GI 381 mmHg, GII 351 mmHg) and significantly decreased during surgery (GI 333 mmHg, GII 291 mmHg) (P < 0.05). No significant differences were found between the groups in both parameters. CONCLUSIONS: FRC significantly decreased from the awake state to surgery in both groups. FRC was not influenced by FIO2 elevation at anesthesia induction.

[Influence of tidal volume on functional residual capacity during general anesthesia].

BACKGROUND: Ventilation with lower tidal volume improves outcome in acute respiratory distress syndrome (ARDS). However, it is questionable if ventilation strategy using lower tidal volumes created for patients with ARDS can be transferred to healthy patients undergoing general anesthesia. We assessed the effects of ventilation with lower tidal volumes and conventional tidal volumes on functional residual capacity (FRC) and Pa(O2)/FI(O2) (P/F) ratio in patients undergoing general anesthesia for upper abdominal surgery. METHODS: We studied 16 patients undergoing general anesthesia for upper abdominal surgery. Patients were randomized to ventilation with low tidal volume group (7 ml x kg(-1) predicted body weight n = 8) or conventional tidal volume group (10 ml x kg(-1) predicted body weight n = 8). We measured FRC and P/F ratio after induction of general anesthesia and start of surgery in both groups. RESULTS: There were no differences in FRC and P/F ratio between ventilation with lower tidal volume group and conventional tidal volume group (P > 0.05), but peak airway pressures with conventional tidal volume group were higher than those with lower tidal volume group only after induction of general anesthesia (P < 0.05). CONCLUSIONS: Lower tidal volumes are better than conventional tidal volumes in view of airway pressure and lung protective strategy during general anesthesia.

[Airway management in a patient with Williams syndrome].

Williams syndrome is characterized by the triad of supravalvular aortic stenosis (SAS), mental retardation and elfin facies. Generally, difficult airway is expected in patients with Williams syndrome by characteristic face. A 26-year-old female with Williams syndrome was scheduled for abdominal myomectomy under general anesthesia. Difficult mask ventilation and tracheal intubation were anticipated because of micrognathia, mandibular retrusion, and a Mallanpati class III airway. Before induction of anesthesia the patient breathed 100% oxygen for 3 minutes. Anesthesia was induced and maintained with propofol, remifentanil and rocuronium bromide. Mask ventilation was easily performed. The direct laryngoscopic view was Cormack grade I and there was no difficulty in the tracheal intubation. After induction of anesthesia, anesthetic course was uneventful. According to the most previous clinical reports in patients with Williams syndrome in Japan, mask ventilation and tracheal intubation were performed easily contrary to preoperative airway assessment. In view of SAS, mental retardation, airway deformity and airway assessment in previous clinical reports, we should select the optimal strategy for airway management in patients with Williams syndrome.

Specific requirement of DRB4, a dsRNA-binding protein, for the in vitro dsRNA-cleaving activity of Arabidopsis Dicer-like 4.

Arabidopsis thaliana Dicer-like 4 (DCL4) produces 21-nt small interfering RNAs from both endogenous and exogenous double-stranded RNAs (dsRNAs), and it interacts with DRB4, a dsRNA-binding protein, in vivo and in vitro. However, the role of DRB4 in DCL4 activity remains unclear because the dsRNA-cleaving activity of DCL4 has not been characterized biochemically. In this study, we biochemically characterize DCL4's Dicer activity and establish that DRB4 is required for this activity in vitro. Crude extracts from Arabidopsis seedlings cleave long dsRNAs into 21-nt small RNAs in a DCL4/DRB4-dependent manner. Immunoaffinity-purified DCL4 complexes produce 21-nt small RNAs from long dsRNA, and these complexes have biochemical properties similar to those of known Dicer family proteins. The DCL4 complexes purified from drb4-1 do not cleave dsRNA, and the addition of recombinant DRB4 to drb4-1 complexes specifically recovers the 21-nt small RNA generation. These results reveal that DCL4 requires DRB4 to cleave long dsRNA into 21-nt small RNAs in vitro. Amino acid substitutions in conserved dsRNA-binding domains (dsRBDs) of DRB4 impair three activities: binding to dsRNA, interacting with DCL4, and facilitating DCL4 activity. These observations indicate that the dsRBDs are critical for DRB4 function. Our biochemical approach and observations clearly show that DRB4 is specifically required for DCL4 activity in vitro.