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PURPOSE: We sought to perform a systematic review and meta-analysis to determine whether indirect laryngoscopy has an advantage over direct laryngoscopy in terms of the tracheal intubation rate, glottic visualization, and intubation time when used by novice operators. METHODS: We extracted adult prospective randomized trials comparing tracheal intubation with indirect vs direct laryngoscopy in novice operators from electronic databases. We extracted the following data from the identified studies: success rate, glottic visualization, and intubation time. Data from each trial were combined via a random-effects model to calculate the pooled relative risk (RR) or weighted mean difference (WMD) with a 95% confidence interval (CI). We also performed a trial sequential analysis. RESULTS: We included 15 articles (17 trials) comprising 2,290 patients in the systematic review. Compared with the direct laryngoscopy, indirect laryngoscopy improved success rate (RR, 1.15; 95% CI, 1.07 to 1.24; P = 0.0002; I2 = 88%), glottic visualization (RR, 1.76; 95% CI, 1.36 to 2.28; P < 0.001; I2 = 85%), and intubation time (WMD, -9.06 sec; 95% CI, -16.4 to -1.76; P = 0.01; I2 = 98%) in tracheal intubation. Trial sequential analysis showed that the total sample size was sufficient to analyze the success rate and intubation time. CONCLUSION: In this systematic review, we found that the tracheal intubation success rate, glottic visualization, and intubation time were improved when novice operators used indirect laryngoscopy rather than direct laryngoscopy. Trial sequential analysis results indicated that the sample size was sufficient for examining the success rate and intubation time. STUDY REGISTRATION: PROSPERO (CRD42022309045); first registered 4 September 2022.

DOI： 10.1007/s12630-023-02642-9

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The optimal administration of inotrope after cardiac surgery is unknown. This study aimed to investigate the impact of postoperative inotrope on clinical outcomes in adult elective cardiac surgery patients. Data from the Blood Pressure and Relative Optimal Target after Heart Surgery in Epidemiologic Registry study were analyzed, employing propensity score considering the hospital of admission. The primary outcome was the length of hospital stay evaluated using quantile regression. Secondary outcomes were kidney injury progression, renal replacement therapy, atrial fibrillation, mortality, mechanical ventilation duration, and length of intensive care unit (ICU) stay. Among 870 patients from 14 ICUs in Japan, 535 received inotropes within 24 h of ICU admission, with usage rates ranging from 40 to 100% among facilities. After propensity score matching, 218 patients were included in each group. The inotrope group had a significantly longer hospital stay compared to the control group (16 days vs. 14 days; median difference 1.78 [95% confidence interval [CI] 0.31-3.24]; p = 0.018). However, no significant differences were observed in the secondary outcomes, except for mechanical ventilation duration. The results of the sensitivity analysis using a mixed-effects quantile regression analysis considering the hospital of admission for length of hospital stay in the original cohort were consistent with the results of the propensity analyses (median difference in days, 2.35 [95% CI, 0.35-4.36]; p = 0.022). The use of inotropes within 24 h of ICU admission in adult elective cardiac surgery patients was associated with an extended hospitalization period of approximately 2 days, without offering any prognostic benefit. Clinical trial registration: UMIN-CTR, https://www.umin.ac.jp/ctr/index-j.htm , UMIN000037074.

DOI： 10.1007/s00380-023-02349-3

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This meta-analysis was performed to determine whether an indirect laryngoscope is more advantageous than a direct laryngoscope for tracheal intubation in the setting of a difficult pediatric airway. Data on the intubation failure and intubation time during tracheal intubation were extracted from prospective and retrospective studies identified through a comprehensive literature search. Data from 10 individual articles (11 trials) were combined, and a DerSimonian and Laird random-effects model was used to calculate either the pooled relative risk (RR) or the weighted mean difference (WMD) and the corresponding 95% confidence interval (CI). Meta-analysis of the 10 articles indicated that the intubation failure of tracheal intubation with an indirect laryngoscope was not significantly different from that of a direct laryngoscope in patients with a difficult airway (RR 0.86, 95% CI 0.51-1.46; p = 0.59; Cochrane's Q = 50.5; I2 = 82%). Intubation time with an indirect laryngoscope was also similar to that with a direct laryngoscope (WMD 4.06 s; 95% CI -1.18-9.30; p = 0.13; Cochrane's Q 39.8; I2 = 85%). In conclusion, indirect laryngoscopes had the same intubation failure and intubation time as direct laryngoscopes in pediatric patients with a difficult airway. Currently, the benefits of indirect laryngoscopes have not been observed in the setting of a difficult pediatric airway.

DOI： 10.3390/children11010060

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Public Library of Science (PLoS)  

Background

Persistent symptoms are reported in patients who survive the initial stage of COVID-19, often referred to as “long COVID” or “post-acute sequelae of SARS-CoV-2 infection” (PASC); however, evidence on their incidence is still lacking, and symptoms relevant to pain are yet to be assessed.

Methods

A literature search was performed using the electronic databases PubMed, EMBASE, Scopus, and CHINAL and preprint servers MedRχiv and BioRχiv through January 15, 2021. The primary outcome was pain-related symptoms such as headache or myalgia. Secondary outcomes were symptoms relevant to pain (depression or muscle weakness) and symptoms frequently reported (anosmia and dyspnea). Incidence rates of symptoms were pooled using inverse variance methods with a DerSimonian-Laird random-effects model. The source of heterogeneity was explored using meta-regression, with follow-up period, age and sex as covariates.

Results

In total, 38 studies including 19,460 patients were eligible. Eight pain-related symptoms and 26 other symptoms were identified. The highest pooled incidence among pain-related symptoms was chest pain (17%, 95% confidence interval [CI], 11%-24%), followed by headache (16%, 95% CI, 9%-27%), arthralgia (13%, 95% CI, 7%-24%), neuralgia (12%, 95% CI, 3%-38%) and abdominal pain (11%, 95% CI, 7%-16%). The highest pooled incidence among other symptoms was fatigue (44%, 95% CI, 32%-57%), followed by insomnia (27%, 95% CI, 10%-55%), dyspnea (26%, 95% CI, 17%-38%), weakness (25%, 95% CI, 8%-56%) and anosmia (19%, 95% CI, 13%-27%). Substantial heterogeneity was identified (I², 50–100%). Meta-regression analyses partially accounted for the source of heterogeneity, and yet, 53% of the symptoms remained unexplained.

Conclusions

The current meta-analysis may provide a complete picture of incidence in PASC. It remains unclear, however, whether post-COVID symptoms progress or regress over time or to what extent PASC are associated with age or sex.

DOI： 10.1371/journal.pone.0250909

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Subcutaneous implantable cardioverter defibrillators (S-ICDs) are occasionally used in combination with other cardiac implantable electronic devices (CIEDs). However, whether the incidence of inappropriate shock increases in patients with S-ICDs and concomitant CIEDs remains unclear. This study aimed to investigate the association between the concomitant use of CIEDs and the incidence of inappropriate shock in patients with current-generation S-ICDs. METHODS: A total of 127 consecutive patients received an S-ICD. Patients were assigned to two groups depending on concomitant use of CIEDs at the time of S-ICD implantation: patients without other CIEDs (non-combined group, 106 patients) and patients with other CIEDs (combined group, 21 patients). CIEDs included pacemakers, implantable cardioverter defibrillators, cardiac resynchronization therapy pacemakers, and cardiac resynchronization therapy defibrillators. The primary outcome was inappropriate shock, defined as a shock other than ventricular arrhythmia. Hazard ratios and 95% confidence intervals were calculated using a time-varying Cox proportional hazards model which was adjusted for age because age differed between the groups and could be a confounder. RESULTS: During a median follow-up period of 2.2 years (interquartile range, 1.0-3.4 years), inappropriate shock events occurred in 17 (16%) and five (19%) patients of the non-combined and combined groups, respectively. While the age-adjusted hazard ratio for inappropriate shock was 24% higher in the combined than in the non-combined group (hazard ratio = 1.24, 95% confidence interval, 0.39-3.97), this difference was insignificant (p = .71). CONCLUSION: The incidence of inappropriate shock did not differ between patients with and without concomitant use of CIEDs, suggesting that S-ICDs could potentially be combined with other CIEDs without increasing the number of inappropriate shocks. Further studies are warranted to confirm the safety and feasibility of concomitant use of S-ICDs and CIEDs.

DOI： 10.1111/pace.14887

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Remote ischemic preconditioning (RIPC) protects organs from ischemia-reperfusion injury. Recent trials showed that RIPC improved gas exchange in patients undergoing lung or cardiac surgery. We performed a systematic search to identify randomized controlled trials involving RIPC in surgery under general anesthesia. The primary outcome was the PaO2/FIO2 (P/F) ratio at 24 h after surgery. Secondary outcomes were A-a DO2, the respiratory index, duration of postoperative mechanical ventilation (MV), incidence of acute respiratory distress syndrome (ARDS), and serum cytokine levels. The analyses included 71 trials comprising 7854 patients. Patients with RIPC showed higher P/F ratio than controls (mean difference [MD] 36.6, 95% confidence interval (CI) 12.8 to 60.4, I2 = 69%). The cause of heterogeneity was not identified by the subgroup analysis. Similarly, A-a DO2 (MD 15.2, 95% CI - 29.7 to - 0.6, I2 = 87%) and respiratory index (MD - 0.17, 95% CI - 0.34 to - 0.01, I2 = 94%) were lower in the RIPC group. Additionally, the RIPC group was weaned from MV earlier (MD - 0.9 h, 95% CI - 1.4 to - 0.4, I2 = 78%). Furthermore, the incidence of ARDS was lower in the RIPC group (relative risk 0.73, 95% CI 0.60 to 0.89, I2 = 0%). Serum TNFα was lower in the RIPC group (SMD - 0.6, 95%CI - 1.0 to - 0.3 I2 = 87%). No significant difference was observed in interleukin-6, 8 and 10. Our meta-analysis suggested that RIPC improved oxygenation after surgery under general anesthesia.Clinical trial number: This study protocol was registered in the University Hospital Medical Information Network (registration number: UMIN000030918), https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000035305.

DOI： 10.1038/s41598-023-44833-w

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PURPOSE: Non-contact continuous respiratory rate monitoring is preferred for early detection of patient deterioration. However, this technique is under development; a gold standard respiratory monitor has not been established. Therefore, this prospective observational method comparison study aimed to compare the measurement accuracy of a non-contact continuous respiratory rate monitor, a microwave Doppler sensor positioned beneath the mattress, with that of other monitors. METHODS: The respiratory rate of intensive care unit patients was simultaneously measured using a microwave Doppler sensor, capnography, thoracic impedance pneumography, and a piezoelectric sensor beneath the mattress. Bias and 95% limits of agreement between the respiratory rate measured using capnography (standard reference) and that measured using the other three methods were calculated using Bland-Altman analysis for repeated measures. Clarke error grid (CEG) analysis evaluated the sensor's ability to assist in correct clinical decision-making. RESULTS: Eighteen participants were included, and 2,307 data points were analyzed. The bias values (95% limits of agreement) of the microwave Doppler sensor, thoracic impedance pneumography, and piezoelectric sensor were 0.2 (- 4.8 to 5.2), 1.5 (- 4.4 to 7.4), and 0.4 (- 4.0 to 4.8) breaths per minute, respectively. Clinical decisions evaluated using CEG analyses were correct 98.1% of the time for the microwave Doppler sensor, which was similar to the performance of the other devices. CONCLUSION: The microwave Doppler sensor had a small bias but relatively low precision, similar to other devices. In CEG analyses, the risk of each monitor leading to inadequate clinical decision-making was low. TRIAL REGISTRATION NUMBER: UMIN000038900, February 1, 2020.

DOI： 10.1007/s10877-023-01081-7

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Language：Japanese   Publisher：(一社)日本てんかん学会  

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OBJECTIVE: Postoperative delirium is common and serious in elderly patients. Several drugs have been proposed as potential prophylactic agents for postoperative delirium. Studies on melatonin receptor agonists showed heterogeneity in age, cognitive function, anesthesia, surgery, interventions, methodologies for assessing outcomes, and results. Our objective was to examine the effect of ramelteon to prevent postoperative delirium in elderly patients, including those with dementia. DESIGN: A stratified, double-blind, randomized, placebo-controlled trial (UMIN000028436, jRCTs031180054). SETTING: Tertiary medical center. PARTICIPANTS: Patients aged older than or equal to 65 years undergoing elective surgery under general anesthesia. INTERVENTION: Ramelteon (8 mg orally) or placebo (lactose) for six nights (the preoperative night and five consecutive nights from postoperative day 1 to 5) at around 9 P.M. MEASUREMENTS: Patients were screened for postoperative delirium using the Confusion Assessment Method for the Intensive Care Unit twice daily until the sixth postoperative day. Patients with positive results were referred to a consultant psychiatrist to establish the diagnosis of delirium. RESULTS: A total of 108 patients were randomly assigned to receive ramelteon (n = 55) or placebo (n = 53). Most of the patients' characteristics were reasonably well-balanced between the two groups. The stratified log-rank test showed no significant difference in preventing postoperative delirium between ramelteon and placebo (χ2 = 0.30, degrees of freedom = 1, p = 0.60). The Cox proportional hazard ratio for ramelteon compared to placebo was 1.40 (95% confidence interval: 0.40-4.85, χ2 for likelihood ratio test = 0.29, degrees of freedom = 1, p = 0.60). CONCLUSION: There was no significant difference in the incidence of postoperative delirium between ramelteon and placebo after general anesthesia in elderly patients.

DOI： 10.1016/j.jagp.2023.07.011

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: In general, caesarean sections are performed under spinal anaesthesia. Hypotension after spinal anaesthesia adversely affects both the mother and fetus. Although several studies have used pulse oximetry-derived indices, such as pulse perfusion index (PI) and Pleth variability index (PVI), to predict hypotension after spinal anaesthesia, the predictive ability of the PI and PVI remain controversial. METHODS AND ANALYSIS: We prepared this protocol following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. We will conduct searches of MEDLINE, Embase, Web of Science, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Clinicaltrial.gov, European Union Clinical Trials Register (EU-CTR), WHO International Clinical Trials Registry Platform (ICTRP) and University Hospital Medical Information Network Clinical Trials Registry (UMIN) from inception until 8 October 2022. We will include retrospective and prospective observational studies and randomised controlled trials that evaluated the predictive ability of PI and PVI for hypotension after spinal anaesthesia for caesarean section, published in any language. We will exclude case reports, case series and animal studies. Two authors will independently scan and select eligible studies and perform data extraction and assessment of risk of bias. We will estimate predictive ability of PI and PVI as indices of hypotension after spinal anaesthesia for caesarean section using the Reitsma-type bivariate random-effects synthesis model and the hierarchical summary receiver operating characteristic curve. We will assess the quality of evidence using the Grading of Recommendation Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION: Ethics approval is not required as the systematic review will use existing published data. The results will be submitted for publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022362596.

DOI： 10.1136/bmjopen-2022-069309

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BACKGROUND: Post-pyloric enteral feeding reduces respiratory complications and shortens the duration of mechanical ventilation. Blind placement of post-pyloric enteral feeding tubes (EFT) in patients with critical illnesses is often the first-line method because endoscopy or fluoroscopy cannot be easily performed at bedside; however, difficult placements regularly occur. We reported an association between the stomach position caudal to spinal level L1-L2, evaluated by abdominal radiographs after placement, and difficult placement; however, this method could not indicate difficulty before EFT placement. The aim of our study was to evaluate the association between stomach position, estimated using computed tomography (CT) images taken before the blind placement of the post-pyloric EFT, and the difficulty of EFT placement. METHODS: Data from patients aged ≥ 20 years who underwent post-pyloric EFT in our intensive care unit were obtained retrospectively. Logistic regression analysis was used to evaluate the association between successful initial EFT placement and explanatory variables, including stomach position estimated by CT. Two cut-off values were used: caudal to L1-L2 based on a previous study and the best cut-off value calculated by the receiver operating characteristic curve. Variable selection was performed backward stepwise using Akaike's Information Criterion. RESULTS: Of the total of 453 patients who were enrolled, the success rate of the initial EFT placement was 43.5%. The adjusted odds ratio for successful initial EFT placement of the stomach position caudal to L1-L2 was 0.61 (95% confidence interval: 0.41-1.07). Logistic regression analysis, including the stomach position caudal to L2-L3, calculated as the best cut-off value, indicated that stomach position was an independent factor for failure of initial EFT placement (adjusted odds ratio, 0.55; 95% confidence interval: 0.33-0.91). CONCLUSIONS: Stomach position evaluated using CT images was associated with successful initial post-pyloric EFT placement. The best cut-off value of the greater curvature of the stomach to predict the success or failure of the first attempt was spinal level L2-L3. Trial registration University Hospital Medical Information Network Clinical Trials Registry (UMIN000046986; February 28, 2022). https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000052151.

DOI： 10.1186/s40560-023-00673-4

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BACKGROUND: Circulatory failure is classified into four types of shock (obstructive, cardiogenic, distributive, and hypovolemic) that must be distinguished as each requires a different treatment. Point-of-care ultrasound (POCUS) is widely used in clinical practice for acute conditions, and several diagnostic protocols using POCUS for shock have been developed. This study aimed to evaluate the diagnostic accuracy of POCUS in identifying the etiology of shock. METHODS: We conducted a systematic literature search of MEDLINE, Cochrane Central Register of Controlled Trials, Embase, Web of Science, Clinicaltrial.gov, European Union Clinical Trials Register, WHO International Clinical Trials Registry Platform, and University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) until June 15, 2022. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and assessed study quality using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Meta-analysis was conducted to pool the diagnostic accuracy of POCUS for each type of shock. The study protocol was prospectively registered in UMIN-CTR (UMIN 000048025). RESULTS: Of the 1553 studies identified, 36 studies were full-text reviewed, and 12 studies with 1132 patients were included in the meta-analysis. Pooled sensitivity and specificity were 0.82 [95% confidence interval (CI) 0.68-0.91] and 0.98 [95% CI 0.92-0.99] for obstructive shock, 0.78 [95% CI 0.56-0.91] and 0.96 [95% CI 0.92-0.98] for cardiogenic shock, 0.90 [95% CI 0.84-0.94] and 0.92 [95% CI 0.88-0.95] for hypovolemic shock, and 0.79 [95% CI 0.71-0.85] and 0.96 [95% CI 0.91-0.98] for distributive shock, respectively. The area under the receiver operating characteristic curve for each type of shock was approximately 0.95. The positive likelihood ratios for each type of shock were all greater than 10, especially 40 [95% CI 11-105] for obstructive shock. The negative likelihood ratio for each type of shock was approximately 0.2. CONCLUSIONS: The identification of the etiology for each type of shock using POCUS was characterized by high sensitivity and positive likelihood ratios, especially for obstructive shock.

DOI： 10.1186/s13054-023-04495-6

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PURPOSE: Postoperative sleep disturbances are common. Although several studies have examined the effect of melatonin on postoperative sleep disturbances, the results have not reached any definitive conclusion. We sought to conduct a systematic review to compare the effects of melatonin and melatonin agonists on postoperative sleep quality with those of placebo or no treatment in adult patients who underwent surgery under general or regional anesthesia. METHODS: We searched MEDLINE, Cochrane Central Register of Controlled Trials, Embase, Web of Science, ClinicalTrials.gov, and the UMIN Clinical Trials Registry up to 18 April 2022. Randomized clinical trials examining the effects of melatonin or melatonin agonists in patients undergoing general or regional anesthesia with sedation for any surgery were eligible for inclusion. The primary outcome was sleep quality measured using a visual analog scale (VAS). The secondary outcomes were postoperative sleep duration, sleepiness, pain, opioid consumption, quality of recovery, and adverse events. A random-effects model was used to combine the results. We assessed study quality with the Cochrane Risk of Bias Tool version 2. We applied a trial sequential analysis to assess the precision of the combined results. RESULTS: Eight studies (516 participants) were analyzed for sleep quality. Of those, four studies used only a short duration of melatonin, either on the night before and the day of surgery or only on the day of surgery. A random-effects meta-analysis showed that melatonin did not improve sleep quality measured by VAS compared with placebo (mean difference, -0.75 mm; 95% confidence interval, -4.86 to 3.35), with low heterogeneity (I2, 5%). Trial sequential analysis revealed that the accrued information size (n = 516) reached the estimated required information size (n = 295). We downgraded the certainty of the evidence because of the high risk of bias. The effect on postoperative adverse events was comparable between the melatonin and control groups. CONCLUSION: Our results indicate that melatonin supplementation does not improve postoperative sleep quality measured with the VAS compared with placebo in adult patients (GRADE: moderate). STUDY REGISTRATION: PROSPERO (CRD42020180167); registered 27 October 2022.

DOI： 10.1007/s12630-023-02442-1

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The excitatory glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) contribute to epileptogenesis. Thirty patients with epilepsy and 31 healthy controls are scanned using positron emission tomography with our recently developed radiotracer for AMPARs, [11C]K-2, which measures the density of cell-surface AMPARs. In patients with focal-onset seizures, an increase in AMPAR trafficking augments the amplitude of abnormal gamma activity detected by electroencephalography. In contrast, patients with generalized-onset seizures exhibit a decrease in AMPARs coupled with increased amplitude of abnormal gamma activity. Patients with epilepsy had reduced AMPAR levels compared with healthy controls, and AMPARs are reduced in larger areas of the cortex in patients with generalized-onset seizures compared with those with focal-onset seizures. Thus, epileptic brain function can be regulated by the enhanced trafficking of AMPAR due to Hebbian plasticity with increased simultaneous neuronal firing and compensational downregulation of cell-surface AMPARs by the synaptic scaling.

DOI： 10.1016/j.xcrm.2023.101020

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Authorship：Lead author,　Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/s12630-023-02442-1

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Other Link： https://link.springer.com/article/10.1007/s12630-023-02442-1/fulltext.html

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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.

DOI： 10.1620/tjem.2023.J018

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

BACKGROUND: It is important to reduce the hemodynamic response during tracheal intubation. We performed a systematic review and meta-analysis of the Airway Scope and Macintosh laryngoscope to determine whether they reduce the hemodynamic responses of heart rate (HR) and mean blood pressure (MBP) after tracheal intubation under general anesthesia. METHODS: We performed a comprehensive literature search of electronic databases for clinical trials comparing hemodynamic response to tracheal intubation. The primary aim of our meta-analyst is to determine if the Airway Scope reduces hemodynamic responses (HR and mean MBP) 60 seconds after tracheal intubation compared to the Macintosh laryngoscope. We expressed pooled differences in hemodynamic responses between the 2 devices as weighted mean differences with 95% confidence intervals. We conducted trial sequential analysis. Secondarily, we investigated the ability of the Airway Scope and Macintosh laryngoscope to reduce hemodynamic responses at 120 seconds, 180 seconds, and 300 seconds after tracheal intubation. RESULTS: We identified clinical trials comparing hemodynamic response via a comprehensive literature search. Of 185 articles found in the search, we selected 8. In comparison to the Macintosh laryngoscope, the Airway Scope significantly reduced HR and MBP at 60 seconds after tracheal intubation (HR; weighted mean difference = -7.29; 95% confidence interval, -10.9 to -3.62; P < .0001; I2 = 57%, MBP; weighted mean difference = -11.5; 95% confidence interval, -20.4 to -2.65; P = .01; I2 = 91%). At the secondary outcome, the Airway Scope significantly reduced the fluctuation of HR after 120 seconds and 180 seconds of tracheal intubation. However, the Airway Scope did not significantly reduce MBP 120 seconds, 180 seconds, and 300 seconds after tracheal intubation. Trial sequential analysis suggested that the total sample size reached the required information size for heart rate. CONCLUSIONS: Our finding suggested that the Airway Scope attenuated hemodynamic responses at 60 seconds after tracheal intubation in comparison with that of the Macintosh laryngoscope. However, the MBP sample size is small and further research is needed.

DOI： 10.1097/md.0000000000033047

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INTRODUCTION: Varicocelectomy is well known to improve the pregnancy outcome of patients with clinical varicoceles in assisted reproductive technologies as well as spontaneous conception. Therefore, this study aimed to evaluate the additional effects of oral antioxidant therapy after varicocelectomy on the pregnancy outcome in the assisted reproductive technology setting. METHODS: This study was a retrospective cohort study. The subjects were couples among whom the male partner had undergone varicocelectomy and was scheduled for subsequent assisted reproductive technology. Pregnancy outcomes were followed retrospectively in 62 couples with male partners who received tocopherol (antioxidant group) and 37 couples who did not (control group). The tocopherol and control groups were assigned dependent on the decision of the physician in charge and the patient's request. The clinical pregnancy rates per couple and embryo transfer, time to pregnancy, and the number of cycles during transfer to pregnancy were evaluated. RESULTS: No significant differences were observed in the pregnancy rate per couple (antioxidant group 70.9% vs. control group 64.9%, P = 0.55) and per embryo transfer (50.4% vs. 39.6%, P = 0.22). Regarding the time to event analyzed by adjusted restricted mean survival time, the mean time to pregnancy was significantly shorter in the antioxidant (tocopherol) group (14.2 vs. 17.4 months, P = 0.025). No significant difference was observed in the embryo transfer cycle to pregnancy (mean embryo transfer cycles: 2.6 vs. 3.0, P = 0.238). CONCLUSIONS: Additional oral tocopherol nicotinate as antioxidant therapy after varicocelectomy was shown to shorten the time to pregnancy. It is recommended that add-on effects be tested in more well-designed randomized controlled trials to examine whether it improves assisted reproductive outcomes.

DOI： 10.3389/frph.2023.1325566

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

This study aimed to evaluate the effectiveness of acupuncture therapy in preventing emergence agitation (EA) in children. A systematic review and meta-analysis were conducted across multiple locations according to the articles searched. Seven databases, including trial registration sites, were searched. A total of six trials were included involving 489 patients; of them, 244 received acupuncture therapy. Randomized clinical trials (RCTs) evaluating the incidence of EA compared with placebo/sham or standard care in children were included. The primary outcome was the incidence of EA, as evaluated using a specific assessment tool. Data about the incidence rate of EA, heterogeneity, quality of trials and evidence, and adverse events were collected. Additionally, data about patient demographic characteristics, type of anesthesia, duration and onset of acupuncture therapy, EA and pain score, time taken for extubation, and post-anesthesia care unit length of stay were collected. The results indicated that the overall incidence of EA in the acupuncture therapy group and the control group was 23.4% and 39.5%, respectively, with no significant difference (risk ratio, 0.62; 95% confidence interval, 0.26-1.48; I2 = 63%). Subgroup analysis showed a significant difference in the overall incidence of EA in the acupuncture therapy and control groups according to surgery type (high-risk vs. low-risk surgery), suggesting that acupuncture therapy may be effective in reducing EA for patients undergoing high-risk surgery. The quality of evidence was downgraded to "very low" due to the study designs, inconsistency, and possible publication bias. In conclusion, this meta-analysis shows that the currently available RCTs are insufficient to determine the effectiveness of acupuncture therapy in preventing EA in children undergoing general anesthesia.

DOI： 10.1371/journal.pone.0286790

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

BACKGROUND: Nasal pressure injury is a serious problem during nasotracheal intubation. We performed this systematic review and meta-analysis to determine whether use of a nasal protection strategy (a protective dressing or a modified fixation method for the tracheal tube) reduces the incidence of nasal pressure injury during nasotracheal intubation. METHODS: Literature searches were performed using three electronic databases. Data from each of the eligible trials were combined, and calculations were made using DerSimonian and Laird random effects models. The pooled effect estimates for nasal pressure injury were evaluated using the relative risk and 95% confidence interval, the Cochrane Q statistic, and the I2 statistic. We also performed trial sequential analysis (TSA) to assess sensitivity to prevent type I error. We separated patients into subgroups to analyze the incidence of nasal pressure injury according to whether a protective dressing or a modified fixation method for the tracheal tube was used. RESULTS: The literature search yielded five eligible trials. Meta-analysis of these trials showed that a nasal protection strategy significantly reduced the incidence of nasal pressure injury during nasotracheal intubation (relative risk (RR) 0.34; 95% confidence interval (CI) 0.21-0.56; P < .0001; Cochrane's Q = 5.86, I2 = 32%). The TSA boundary for futility could not be calculated because of an insufficient sample size. In subgroup analysis, both methods significantly reduced the incidence of nasal pressure injury during nasotracheal intubation. CONCLUSIONS: The findings of this meta-analysis suggest that a nasal protection strategy significantly reduces the incidence of nasal pressure injury during nasotracheal intubation. During nasotracheal intubation, the use of a protective dressing or modified fixation method for the tracheal tube can prevent to the incidence of nasal pressure injuries. However, the number of samples in our meta-analysis was too small for TSA and further studies are required. TRIALS REGISTRATION: PROSPERO (International Prospective Register of Systematic Reviews; registration number 252091).

DOI： 10.1097/md.0000000000030638

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This research aimed to produce a coherent ranking of the effectiveness of intubation devices in pediatric patients using network meta-analysis (NMA). We searched the electric databases for prospective randomized studies that compared different tracheal intubation devices in pediatric patients. The primary outcome was intubation failure at the first attempt. Secondary outcomes were glottic visualization and intubation time. The statistical analysis performed used DerSimonian and Laird random-effects models. Frequentist network meta-analysis was conducted, and network plots and network league tables were produced. Subgroup analysis was performed after excluding rigid-fiberscope-type indirect laryngoscopes. Thirty-four trials comparing 13 devices were included. Most laryngoscopes had the same intubation failure rate as the Macintosh reference device. Only the Truview PCD™ had a significantly higher intubation failure rate than the Macintosh (odds ratio 4.78, 95% confidence interval 1.11-20.6) The highest-ranking laryngoscope was the Airtaq™ (P score, 0.90), and the AirwayScope™, McGrath™, and Truview EVO2™ ranked higher than the Macintosh. The Bullard™ had the lowest ranking (P score, 0.08). All laryngoscopes had the same level of glottic visualization as the Macintosh and only the C-MAC™ had a significantly shorter intubation time. Intubation time was significantly longer when using the GlideScope™, Storz DCI™, Truview PCD™, or Bullard™ compared with the Macintosh. P score and ranking of devices in the subgroup analyses were similar to those in the main analysis. We applied NMA to create a consistent ranking of the effectiveness of intubation devices in pediatric patients. The findings of NMA suggest that there is presently no laryngoscope superior to the Macintosh laryngoscope in terms of tracheal intubation failure rate and glottic visualization in pediatric patients.

DOI： 10.3390/children9091280

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Language：Japanese   Publisher：国際医療福祉大学学会  

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PURPOSE: Perioperative depressive symptoms are associated with poor postoperative quality of life (QOL), leading to prolonged hospital stays, and delayed return to society. Previous studies show that physical and mental states change on the third day after surgery, and there is a correlation between quality of recovery (QoR) on this day and QOL at 3 months after surgery. QoR after surgery is an important indicator of postoperative QOL. However, there are no reports on the association between depressive symptoms, and postoperative QoR. Therefore, the study purpose was to clarify the relationship between depressive symptoms in perioperative cancer patients during the prehospitalization waiting period, and QoR on the third postoperative day. DESIGN: This was a prospective cohort study. METHODS: We examined whether depressive symptoms during the prehospitalization waiting period were related to QoR on day 3 after surgery in perioperative cancer patients. Subjects were patients with primary tumors who underwent surgery under general anesthesia. Subjects completed self-administered questionnaires during the prehospitalization waiting period and on postoperative day 3. The presence and/or absence of depressive symptoms was measured using the Hospital Anxiety and Depression Scale. Subjects were divided into two groups: depressive symptoms or non-depressive symptoms. Postoperative QoR was determined using the QoR-40 questionnaire and we calculated the rate of change in QoR-40 global and dimension scores from preoperation to postoperation. FINDINGS: 231 individuals met the inclusion criteria and agreed to participate in the study. Of these, 173 were included in the analysis. Only the rate of change in emotional state differed significantly between groups (P = .022). Both global and dimension QoR-40 scores were lower in the depressive symptoms group than in the non-depressive symptoms group. CONCLUSIONS: These findings demonstrate the need to provide both psychological and physical support continuously from the preoperative to early postoperative stage for cancer patients with depressive symptoms in the prehospitalization waiting period.

DOI： 10.1016/j.jopan.2021.11.007

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BACKGROUND: Patients with inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, might present difficulties in achieving postoperative analgesia. Prior studies have suggested that patients with IBD undergoing major abdominal surgery require higher doses of perioperative opioids than do patients without IBD. Considering patients with IBD potentially require high-dose opioids, identifying those requiring higher opioid doses will allow clinicians to optimize the perioperative opioid dose and avoid insufficient pain management or complications of opioid overdose. Therefore, we conducted this study to identify predictive factors that might influence postoperative opioid consumption in patients with IBD. METHODS: This single-center, historical cohort study reviewed the medical records of all patients admitted to the IBD center of our institution for surgery and who used intravenous fentanyl patient-controlled analgesia (PCA) after open abdominal surgery between June 2013 and April 2017. Ultimately, 179 patients were enrolled in the analysis. Variables expected to influence and/or represent pain, analgesia, inflammation, disease condition, and extent of surgery were selected as potential explanatory variables for predicting postoperative opioid consumption. Multivariable linear regression analysis was used to examine the effect of independent variables on postoperative fentanyl consumption. RESULTS: Of the nine predictive variables selected using the stepwise-selection method, eight were significant. Intraoperative fentanyl consumption, current smoking, ulcerative colitis, administration of biologics during the month before surgery, and the use of supplementary analgesics had a significant increasing effect on postoperative fentanyl consumption, whereas droperidol concentration in the PCA solution, age, and diabetes mellitus had a significant decreasing effect. Preoperative use of opioids was a non-significant variable. The adjusted coefficient of determination was 0.302. CONCLUSIONS: Intraoperative fentanyl consumption, current smoking, ulcerative colitis, administration of biologics during the month before surgery, and the use of supplementary analgesics had a significant increasing effect, whereas droperidol concentration in the PCA solution, age, and diabetes mellitus had a significant decreasing effect on postoperative fentanyl consumption. These factors should be considered when adopting postoperative intravenous fentanyl PCA administration for patients with IBD. TRIAL REGISTRATION: Registry: UMIN Clinical Trials Registry. CLINICAL TRIAL NUMBER: UMIN000031198 . Date of registration: February 8, 2018.

DOI： 10.1186/s12871-022-01606-8

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PURPOSE: In recent years, various types of indirect laryngoscopes have been developed. Nevertheless, no conclusions have been drawn about which type of indirect laryngoscope is most effective for tracheal intubation. We performed a systematic review and meta-analysis to determine whether the Airtraq® or the GlideScope® is more effective for tracheal intubation. METHODS: We extracted studies of adult prospective randomized trials comparing tracheal intubation between the Airtraq and GlideScope. An electronic database was used to extract the studies included in our meta-analysis. We extracted the following data from the identified studies: success rate, glottic visualization, and intubation time. Data from each trial were combined via a random-effects model for calculation of pooled relative risk (RR) or weighted mean difference (WMD) with a 95% confidence interval (CI). We also performed trial sequential analysis. RESULTS: We included eight trials comprising 571 patients for review. Compared with the GlideScope, Airtraq did not improve success rate, glottic visualization, or intubation time in tracheal intubation (success rate: RR, 0.98; 95% CI, 0.91 to 1.05; P = 0.58; I2 = 65%; glottic visualization: RR, 1.07; 95% CI, 0.88 to 1.29; P = 0.69; I2 = 64%; and intubation time: WMD, 1.4 seconds ; 95% CI, -6.2 to 9.1; P = 0.72; I2 = 96%). The quality of evidence was graded as "very low." Trial sequential analysis showed that total sample size did not reach the required information size for all parameters. CONCLUSION: In this meta-analysis, use of the Airtraq indirect laryngoscope did not result in improved success rate, glottic visualization, or intubation time in tracheal intubation compared with the GlideScope. Trial sequential analysis suggests that further studies are necessary to confirm these findings.

DOI： 10.1007/s12630-022-02217-0

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Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicits varying degrees of protective immunity conferred by neutralizing antibodies (nAbs). In this study, we report the persistence of nAb responses over 12 months after infection despite their decreasing trend noticed from 6 months. Methods: The study included sera from 497 individuals who had been infected with SARS-CoV-2 between January and August 2020. Samples were collected at 6 and 12 months after onset. The titers of immunoglobulin (Ig)G to the viral nucleocapsid protein (NP) and receptor-binding domain (RBD) of the spike protein were measured by chemiluminescence enzyme immunoassay. The nAb titer was determined using lentivirus-based pseudovirus or authentic virus. Results: Antibody titers of NP-IgG, RBD-IgG, and nAbs were higher in severe and moderate cases than in mild cases at 12 months after onset. Although the nAb levels were likely to confer adequate protection against wild-type viral infection, the neutralization activity to recently circulating variants in some of the mild cases (~30%) was undermined, implying the susceptibility to reinfection with the variants of concerns (VOCs). Conclusions: Coronavirus disease 2019 convalescent individuals have robust humoral immunity even at 12 months after infection albeit that the medical history and background of patients could affect the function and dynamics of antibody response to the VOCs.

DOI： 10.1093/ofid/ofab626

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OBJECTIVE: Phase-amplitude coupling between high-frequency (≥150 Hz) and delta (3-4 Hz) oscillations - modulation index (MI) - is a promising, objective biomarker of epileptogenicity. We determined whether sevoflurane anesthesia preferentially enhances this metric within the epileptogenic zone. METHODS: This is an observational study of intraoperative electrocorticography data from 621 electrodes chronically implanted into eight patients with drug-resistant, focal epilepsy. All patients were anesthetized with sevoflurane during resective surgery, which subsequently resulted in seizure control. We classified 'removed' and 'retained' brain sites as epileptogenic and non-epileptogenic, respectively. Mixed model analysis determined which anesthetic stage optimized MI-based classification of epileptogenic sites. RESULTS: MI increased as a function of anesthetic stage, ranging from baseline (i.e., oxygen alone) to 2.0 minimum alveolar concentration (MAC) of sevoflurane, preferentially at sites showing higher initial MI values. This phenomenon was accentuated just prior to sevoflurane reaching 2.0 MAC, at which time, the odds of a site being classified as epileptogenic were enhanced by 86.6 times for every increase of 1.0 MI. CONCLUSIONS: Intraoperative MI best localized the epileptogenic zone immediately before sevoflurane reaching 2.0 MAC in this small cohort of patients. SIGNIFICANCE: Prospective, large cohort studies are warranted to determine whether sevoflurane anesthesia can reduce the need for extraoperative, invasive evaluation.

DOI： 10.1016/j.clinph.2021.11.004

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Cold Spring Harbor Laboratory  

Rationale:
Acute respiratory distress syndrome (ARDS) with COVID-19 is aggravated by hyperinflammatory responses even after passing the peak of viral load. However, the underlying mechanisms remain unclear.

Objectives :
Here, we assess whether alveolar epithelial cell necrosis and subsequent releases of damage associated molecular patterns (DAMPs) at an early disease stage aggravate ARDS with COVID-19

Methods:
In patients with COVID-19 with and without ARDS and healthy adults, serum levels of the following were quantified: an epithelial total cell death marker, cytokeratin18-M65; an epithelial apoptosis marker, CK18-M30; HMGB-1; and alveolar epithelial and endothelial injury markers, sRAGE, angiopoietin-2, and surfactant protein-D. Molecular mechanisms of alveolar epithelial cell death and effects of HMGB-1 neutralization on alveolar tissue injury were assessed using a mouse model of COVID-19-induced ARDS.

Measurements and main results:
The levels of CK18-M65, CK18-M30, and alveolar tissue injury markers were elevated in early stages of ARDS. The median M30/M65 ratio, an epithelial apoptosis indicator, was 31.50% in patients with ARDS, a value significantly lower than that of non-ARDS patients or healthy subjects. Serum levels of HMGB-1, one of DAMPs released from necrotic cells, were also significantly elevated in ARDS versus non-ARDS patients. In a COVID-19-induced ARDS mouse model, alveolar epithelial cell necrosis involved two forms of programmed necrosis, necroptosis and pyroptosis. Finally, neutralization of HMGB-1 attenuated alveolar tissue injury in the mouse model.

Conclusions:
Necrosis, including necroptosis and pyroptosis, seems to be the primary form of alveolar epithelial cell death, and subsequent release of DAMPs is a potential driver of COVID-19-induced ARDS.

DOI： 10.1101/2022.01.23.22269723

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INTRODUCTION: In geriatric patients, hypotension is often reported after general anesthesia induction using propofol. Remimazolam is a novel short-acting sedative. However, the incidence of hypotension after general anesthesia induction using remimazolam in geriatric patients remains unclear. This study aims to compare the incidence of hypotension associated with remimazolam and propofol in patients aged ≥80 years. METHODS: This single-center, double-blind, randomized, two-arm parallel group, standard treatment-controlled, interventional clinical trial will include 90 patients aged ≥80 years undergoing elective surgery under general anesthesia who will be randomized to receive remimazolam or propofol for induction. The primary outcome is the incidence of hypotension after general anesthesia induction, occurring between the start of drug administration and 3 min after intubation. We define hypotension as mean blood pressure <65 mmHg. The primary outcome will be analyzed using the full analysis set. The incidence of hypotension in the two groups will be compared using the Mantel-Haenszel χ2 test. Subgroup analysis of the primary outcome will be performed based on the Charlson comorbidity index, clinical frailty scale, hypertension in the ward, and age. Secondary outcomes will be analyzed using the Fisher's exact test, Student's t test, and Mann-Whitney U test, as appropriate. Logistic regression analysis will be performed to explore the factors associated with the incidence of hypotension after anesthesia induction. DISCUSSION: Our trial will determine the efficacy of remimazolam in preventing hypotension and provide evidence on the usefulness of remimazolam for ensuring hemodynamic stability during general anesthesia induction in geriatric patients. TRIAL REGISTRATION: The study has been registered with UMIN Clinical Trials Registry (UMIN000042587), on June 30, 2021.

DOI： 10.1371/journal.pone.0275451

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Pain, autonomic distress, and emergence agitation occur commonly in children undergoing general anesthesia. While acupuncture therapy has been reported to effectively reduce such pain and autonomic distress in children, its effect in preventing emergence agitation remains unclear. Therefore, we will conduct a systematic review and meta-analysis with trial sequential analysis to evaluate the effect of acupuncture therapy in preventing emergence agitation in children undergoing general anesthesia. Methods and analysis This protocol was prepared according to the 2015 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) for Protocols guidelines. We will conduct a search for randomized controlled trials that evaluated the effect of acupuncture therapy in preventing emergence agitation. The following databases will be searched for relevant articles: MEDLINE, CENTRAL, Embase, and Web of Science; four pre-registration sites will be accessed from inception to April 1, 2021. No language restrictions will be applied. Two authors will independently scan and select eligible studies, extract the data, and assess the risk of bias. The incidence of emergence agitation will be combined as a risk ratio with a 95% confidence interval using a random-effect model. The I2 statistics will be used to assess heterogeneity. We will evaluate the quality of the clinical trials using the Cochrane methodology and assess the quality of evidence using the Grading of Recommendation Assessment, Development, and Evaluation approach. If appropriate, a trial sequential analysis will be performed. Expected outcomes This meta-analysis will be the first to evaluate the effect of acupuncture therapy in preventing emergence agitation in children. The findings from this meta-analysis have the potential to reveal pivotal factors that affect the clinical effect of acupuncture therapy, thereby supporting the optimization of acupuncture therapy for emergence agitation. Protocol registration University Hospital Medical Information Network Clinical Trials Registry (UMIN000040775).

DOI： 10.1371/journal.pone.0264197

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BACKGROUND: Trans-jejunal nutrition via a post-pyloric enteral feeding tube has a low risk of aspiration or reflux; however, placement of the tube using the blind method can be difficult. Assistive devices, such as fluoroscopy or endoscopy, are useful but may not be suitable for patients with hemodynamic instability or severe respiratory failure. The aim of this study was to explore factors associated with first-pass success in the blind placement of post-pyloric enteral feeding tubes in critically ill patients. METHODS: Data were obtained retrospectively from the medical records of adult patients who had a post-pyloric enteral feeding tube placed in the intensive care unit between January 1, 2012, and December 31, 2018. Logistic regression analysis was performed to assess the association between first-pass success and the independent variables. For logistic regression analysis, the following 13 variables were defined as independent variables: age, sex, height, fluid balance from baseline, use of sedatives, body position during the procedure, use of cardiac assist devices, use of prokinetic agents, presence or absence of intestinal peristalsis, postoperative cardiovascular surgery, use of renal replacement therapy, serum albumin levels, and position of the greater curvature of the stomach in relation to spinal levels L1 - L2. RESULTS: Data obtained from 442 patients were analyzed. The first-pass success rate was 42.8% (n = 189). Logistic regression analysis demonstrated that the position of the greater curvature of the stomach cephalad to L1 - L2 was only associated with successful placement (odds ratio for first-pass success, 0.62; 95% confidence interval: 0.40 - 0.95). CONCLUSIONS: In critically ill patients, the position of the greater curvature of the stomach caudal to L1 - L2 may be associated with a lower first-pass success rate of the blind method for post-pyloric enteral feeding tube placement. Further studies are needed to verify our results because the position of the stomach was estimated by radiographs after enteral feeding tube placement. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry (UMIN000036549; April 20, 2019).

DOI： 10.1186/s40560-021-00577-1

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: The circadian rhythm of melatonin secretion is disturbed after general anaesthesia, leading to postoperative sleep disturbance. Small studies investigating the preventive effect of melatonin administration on postoperative sleep disturbance have not reached any conclusions. Therefore, we will conduct a systematic review and meta-analysis to obtain conclusive results. METHODS AND ANALYSIS: We prepared this protocol following the 2015 Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols guidelines. We will conduct a search for randomised controlled trials that evaluated the effect of melatonin and melatonin agonists on postoperative sleep quality in adult patients undergoing general anaesthesia or regional anaesthesia with sedation. We will exclude patients undergoing regional anaesthesia without sedation. Relevant studies will be searched in the following eight databases: MEDLINE, the Cochrane Central Register of Controlled Trials, Embase, Web of Science and four preregistration sites from inception to 1 January 2021. No language restrictions will be applied. Two authors will independently scan and select eligible studies and perform data extraction and assessment of the risk of bias. The Visual Analogue Scale scores for sleep quality will be combined as the mean difference with a 95% CI using a random-effect model; we will use I2 to assess heterogeneity. We will evaluate the quality of trials using the Cochrane methodology and assess the quality of evidence using the Grading of Recommendation Assessment, Development and Evaluation approach. If appropriate, trial sequential analysis will be performed. ETHICS AND DISSEMINATION: No ethical approval is required for this meta-analysis, as it does not include individual patient data. We will disseminate the results of this meta-analysis in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020180167.

DOI： 10.1136/bmjopen-2020-047858

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The uncontrolled spread of the COVID-19 pandemic has led to the emergence of different SARS-CoV-2 variants across the globe. The ongoing global vaccination strategy to curtail the COVID-19 juggernaut, is threatened by the rapidly spreading Variants of Concern (VOC) and other regional mutants, which are less responsive to neutralization by infection or vaccine derived antibodies. We have previously developed the hiVNT system which detects SARS-CoV-2 neutralizing antibodies in sera in less than three hours. In this study, we modify the hiVNT for rapid qualitative screening of neutralizing antibodies (nAb) to multiple VOC of SARS-CoV-2, and assess the neutralizing efficacy of the BNT162b2 mRNA vaccine on seven epidemiologically relevant SARS-CoV-2 variants. Here we show that the BNT162b2 mRNA vaccine can activate humoral immunity against the major SARS-CoV-2 mutants that are currently in circulation. Albeit a small sample size, we observed that one dose of vaccine was sufficient to elicit a protective humoral response in previously infected people. Using a panel of seven SARS-CoV-2 variants and a single prototype virus, our modified hiVNT would be useful for large-scale community wide testing to detect protective immunity that may confer vaccine/immune passport in the ongoing COVID-19 pandemic.

DOI： 10.1093/jmcb/mjab050

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PURPOSE: We aimed to compare the beneficial and harmful effects of opioids used as adjuncts to local anesthetics in patients undergoing cesarean section under spinal anesthesia. METHODS: We searched electronic databases and ClinicalTrials.gov from their inception until March, 2021 without language restrictions. The primary outcome was the complete analgesia duration (Time to VAS > 0). Data were synthesized using the Bayesian random-effects model. Evidence confidence was evaluated using the Confidence In Network Meta-Analysis. RESULTS: We identified 66 placebo-controlled randomized controlled trials (RCTs) comprising 4400 patients undergoing elective cesarean section. Compared with the placebo, intrathecal opioids (fentanyl, sufentanil, and morphine) significantly prolonged the analgesia duration by 96, 96, and 190 min, respectively (mean difference). Despite morphine ranking first, opioid efficacy was similar; the results were inconsistent with respect to other analgesic outcomes. Except for diamorphine, all opioids were associated with significant increases in the pruritus incidence. Sufentanil and morphine were associated with increases in the respiratory depression incidence. CONCLUSIONS: We confirmed that intrathecal opioids benefit postoperative analgesia. Although morphine seems to be the most appropriate agent, some results were inconsistent, and the evidence confidence was often moderate or low, especially for adverse outcomes. Well-designed RCTs with an evidence-based approach are imperative for determining the most appropriate opioid for cesarean sections.

DOI： 10.1007/s00540-021-02980-2

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Continuous monitoring of the respiratory rate is crucial in an acute care setting. Contact respiratory monitoring modalities such as capnography and thoracic impedance pneumography are prone to artifacts, causing false alarms. Moreover, their cables can restrict patient behavior or interrupt patient care. A microwave Doppler sensor is a novel non-contact continuous respiratory rate monitor. We compared respiratory rate measurements performed with a microwave Doppler sensor mounted on the ceiling of an intensive care unit with those obtained by conventional methods in conscious and spontaneously breathing patients. Participants' respiratory rate was simultaneously measured by visual counting of chest wall movements for 60 s; a microwave Doppler sensor; capnography, using an oxygen mask; and thoracic impedance pneumography, using electrocardiogram electrodes. Bland-Altman analysis for repeated measures was performed to calculate bias and 95% limits of agreement between the respiratory rate measured by visual counting (reference) and that measured by each of the other methods. Among 52 participants, there were 336 (microwave Doppler sensor), 275 (capnography), and 336 (thoracic impedance pneumography) paired respiratory rate data points. Bias (95% limits of agreement) estimates were as follows: microwave Doppler sensor, 0.3 (- 6.1 to 6.8) breaths per minute (bpm); capnography, - 1.3 (- 8.6 to 6.0) bpm; and thoracic impedance pneumography, 0.1 (- 4.4 to 4.7) bpm. Compared to visual counting, the microwave Doppler sensor showed small bias; however, the limits of agreement were similar to those observed in other conventional methods. Our monitor and the conventional ones are not interchangeable with visual counting.Trial registration number: UMIN000032021, March/30/2018.

DOI： 10.1007/s10877-021-00733-w

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DOI： 10.1186/s13054-021-03596-4

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND AND OBJECTIVES: Although previous reports have shown intraocular pressure changes during robotic-assisted laparoscopic prostatectomy, they did not discuss the time course of changes or the timing of the largest change. We conducted this study to quantify pressure changes over time in patients assuming the steep Trendelenburg position during robotic-assisted laparoscopic prostatectomy. METHODS: Twenty-one men were enrolled. Intraocular pressure was measured before anesthesia induction in the supine position (T0); 30 (T1), 90 (T2), and 150 minutes after assuming the Trendelenburg position (T3); and 30 minutes after reassuming the supine position (T4). End-tidal carbon dioxide and blood pressure were also recorded. To compare intraocular pressure between the time points, we performed repeated-measures analysis of variance. A mixed-effects multivariate regression analysis was conducted to adjust for confounding factors. RESULTS: The mean (standard deviation) intraocular pressure was 18.3 (2.4), 23.6 (3.0), 25.1 (3.1), 25.3 (2.2), and 18.1 (5.0) mmHg at T0, T1, T2, T3, and T4, respectively. The mean intraocular pressure was higher at T1, T2, and T3 than at T0 (p < 0.0001 for all). There was no significant difference between T0 and T4, and between T3 and T2 (p > 0.99 for both). CONCLUSIONS: The Trendelenburg position during robotic-assisted laparoscopic prostatectomy increased intraocular pressure. The increase was moderate at 90 minutes after the position was assumed, with the value being approximately 7 mmHg higher than the baseline value. The baseline intraocular pressure was restored at 30 minutes after the supine position was reassumed. TRIAL REGISTRATION: UMIN ID 000014973 DATE OF REGISTRATION: August 27, 2014.

DOI： 10.1016/j.bjane.2021.02.041

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BACKGROUND: The aim of this meta-analysis with trial sequential analysis (TSA) was to evaluate the effect of a polyurethane (PU) tracheal tube cuff on the prevention of ventilator-associated pneumonia (VAP). METHODS: We performed a systematic search using the MEDLINE database through PubMed, Cochrane Central Register of Controlled Trial, SCOPUS, and Web of Science.Randomized controlled trials comparing the incidence of VAP and clinically relevant outcomes between PU cuff tubes and polyvinyl chloride (PVC) cuff tubes in adult patients. Two authors independently extracted study details, patient characteristics, and clinical outcomes such as incidence of VAP, bacterial colonization of tracheal aspirate, duration of mechanical ventilation, ICU stay, and ICU mortality. RESULTS: From 309 studies identified as potentially eligible, six studies with 1226 patients were included in this meta-analysis. All studies compared the incidence of VAP between PU cuffs and PVC cuffs. Use of a PU cuff was not associated with a reduction in VAP incidence (RR = 0.68; 95% CI, 0.45-1.03) with significant statistical heterogeneity (I2 = 65%). The quality of evidence was "very low." According to the TSA, the actual sample size was only 15.8% of the target sample size, and the cumulative Z score did not cross the trial sequential monitoring boundary for benefit. No positive impact was reported for the other relevant outcomes for PU cuffs. CONCLUSIONS: The use of a PU cuff for mechanical ventilation did not prevent VAP. Further trials with a low risk of bias need to be performed.

DOI： 10.1097/MD.0000000000024906

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OBJECTIVE: The authors performed a meta-analysis to determine if vasopressin improves hypotension more than norepinephrine under general anesthesia. DESIGN: Meta-analysis. SETTING: Operating room. PATIENTS: Patients who underwent surgery, with general anesthesia. INTERVENTIONS: Administration of vasopressin or norepinephrine in order to increase blood pressure. MEASUREMENTS AND MAIN RESULTS: The primary outcome of this study was to determine if vasopressin increased mean blood pressure more effectively compared with norepinephrine for patients under general anesthesia. The secondary outcome was to see if vasopressin increased heart rate (HR), central venous pressure (CVP), cardiac output (CO), and cardiac index (CI) more significantly compared with norepinephrine under general anesthesia. The authors calculated the weighted mean difference, with 95% confidence interval (CI) using the random-effects model, and calculated the required information size (RIS) by performing trial sequential analysis (TSA). The authors selected 6 studies for analysis. Vasopressin did not improve hypotension compared with norepinephrine under general anesthesia. (weighted mean difference = -0.84 mmHg, 95% CI: -5.90 to 4.23, p = 0.75, Cochran Q = 24.6, I2 = 84%) In TSA, only 35.5% of RIS was achieved. Similarly, vasopressin and norepinephrine were not significantly different in terms of HR, CVP, CO, and CI. In TSA, only 23.7% of the RIS was reached for HR but RIS was almost achieved for CVP and CO. CONCLUSIONS: Vasopressin did not improve hypotension compared with norepinephrine under general anesthesia. The RIS was not reached in TSA, and Grading of Recommendations Assessment, Development and Evaluation is very low. Therefore, further research is needed to reach more robust conclusions.

DOI： 10.1053/j.jvca.2020.08.011

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Objective: There is scarce evidence regarding the long-term persistence of neutralizing antibodies among coronavirus disease 2019 (COVID-19) survivors. This study determined neutralizing antibody titers (NT50) and antibodies against spike protein (SP) or nucleocapsid protein (NP) antigens approximately 6 months after the diagnosis of COVID-19. Methods: COVID-19 survivors in Japan were recruited. Serum samples and data related to patients' characteristics and COVID-19 history were collected. NT50 and titers of antibodies against NP and SP antigens were measured at 20-32 weeks after the first positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test results. Factors associated with NT50 were identified using the multivariable linear regression and the correlations among NT50 and titers of immunoglobulin G (IgG) and total immunoglobulins (Igs) against NP and SP were assessed by Spearman's correlation. Results: Among 376 participants (median [range] days after testing positive for SARS-CoV-2, 180 (147-224); median [range] years of age, 50 (20-78); 188 [50%] male), most tested positive for NT50 (n = 367, 98%), SP-IgG (n = 344, 91%), SP-total Ig (n = 369, 98%), NP-IgG (n = 314, 84%), and NP-total Ig (n = 365, 97%). Regression analysis indicated that higher BMI, fever, and the requirement of mechanical ventilation or extracorporeal membrane oxygenation were significantly associated with higher NT50. Anti-SP antibodies correlated moderately with NT50 (Spearman's correlation: 0.63 for SP IgG; 0.57 for SP-total Ig), while the correlation was weak for anti-NP antibodies (0.37 for NP IgG; 0.32 for NP-total Ig). Conclusions: Most COVID-19 survivors had sustained neutralizing antibodies and tested positive for SP-total Ig and NP-total Ig approximately 6 months after infection.

DOI： 10.3389/fmicb.2021.661187

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PURPOSE: Patients undergo dilatation and evacuation for abortion or miscarriage. However, bleeding is sometimes problematic. Despite reports on the association between volatile anesthetics and increased bleeding during the procedure, firm evidence is lacking. Therefore, we conducted a systematic review and meta-analysis to compare the effects of volatile anesthetics and propofol on the amount of bleeding in patients undergoing dilatation and evacuation. METHODS: We conducted a systematic search of four databases, namely PubMed, Embase, Cochrane Central Register of Controlled Trials databases, and Web of Science (Clarivate Analytics), from their respective inception to April 2021. Moreover, we searched two trial registration sites. The inclusion criterion was randomized controlled trials of patients who underwent dilatation and evacuation under general anesthesia using volatile anesthetics or propofol. The primary outcome was the amount of perioperative bleeding. The mean difference of the bleeding was combined using a random-effects model. The I2 statistic was used to assess heterogeneity. We assessed risk of bias with Cochrane domains. We controlled type I and II errors due to sparse data and repetitive testing with Trial Sequential Analysis. We assessed the quality of evidence with GRADE. RESULTS: Five studies were included in the systematic review. The amount of bleeding was compared in four studies and was higher in the volatile anesthetic group, with a mean difference of 164.7 ml (95% confidence interval, 43.6 to 285.7; p = 0.04). Heterogeneity was considerable, with an I2 value of 97%. Two studies evaluated the incidence of significant bleeding, which was significantly higher in the volatile anesthetic group (RR, 2.42; 95% confidence interval, 1.04-5.63; p = 0.04). CONCLUSION: Choosing propofol over volatile anesthetics during dilatation and evacuation might reduce bleeding and the incidence of excessive bleeding. However, the quality of the evidence was very low. This necessitates further trials with a low risk of bias. TRIAL REGISTRATION: PROSPERO (CRD42019120873).

DOI： 10.1371/journal.pone.0261494

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Immature neurons dominantly express the Na+-K+-2Cl- cotransporter isoform 1 (NKCC1) rather than the K+-Cl- cotransporter isoform 2 (KCC2). The intracellular chloride ion concentration ([Cl-]i) is higher in immature neurons than in mature neurons; therefore, γ-aminobutyric acid type A (GABAA) receptor activation in immature neurons does not cause chloride ion influx and subsequent hyperpolarization. In our previous work, we found that midazolam, benzodiazepine receptor agonist, causes less sedation in neonatal rats compared to adult rats and that NKCC1 blockade by bumetanide enhances the midazolam-induced sedation in neonatal, but not in adult, rats. These results suggest that GABA receptor activation requires the predominance of KCC2 over NKCC1 to exert sedative effects. In this study, we focused on CLP290, a novel KCC2-selective activator, and found that midazolam administration at 20 mg/kg after oral CLP290 intake significantly prolonged the righting reflex latency even in neonatal rats at postnatal day 7. By contrast, CLP290 alone did not exert sedative effects. Immunohistochemistry showed that midazolam combined with CLP290 decreased the number of phosphorylated cAMP response element-binding protein-positive cells in the cerebral cortex, suggesting that CLP290 reverted the inhibitory effect of midazolam. Moreover, the sedative effect of combined CLP290 and midazolam treatment was inhibited by the administration of the KCC2-selective inhibitor VU0463271, suggesting indirectly that the sedation-promoting effect of CLP290 was mediated by KCC2 activation. To our knowledge, this study is the first report showing the sedation-promoting effect of CLP290 in neonates and providing behavioral and histological evidence that CLP290 reverted the sedative effect of GABAergic drugs through the activation of KCC2. Our data suggest that the clinical application of CLP290 may provide a breakthrough in terms of midazolam-resistant sedation.

DOI： 10.1371/journal.pone.0248113

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Purpose of this prospective, double-blind, parallel-group, placebo-controlled, randomised clinical trial was to confirm our hypothesis that ramelteon has a preventive effect on emergence agitation after general anaesthesia in children. Patients aged 18 to 119 months (ASA physical status 1 or 2), scheduled to undergo tonsillectomy under general anaesthesia, were randomly allocated to the ramelteon or placebo group. Before general anaesthesia induction, patients in the ramelteon group received 0.1 mg kg-1 of ramelteon dissolved in 5 mL of lactose-containing syrup. The patients in the placebo group received the same amount of syrup alone. The Paediatric Anaesthesia Emergence Delirium score was calculated every 5 min after awakening. The primary outcome was the incidence of emergence agitation (Paediatric Anaesthesia Emergence Delirium score ≥ 10). Paediatric Anaesthesia Emergence Delirium scores, post-operative vomiting incidence, pain scores, and adverse events were secondary outcomes. Fifty patients were enrolled. Forty-eight patients were analysed. There was no significant between-group difference in the incidence of emergence agitation (67% in both groups; risk ratio, 1.0; 95% CI 0.67-1.49; P > 0.99) or any of the secondary outcomes. Our results suggest that 0.1 mg kg-1 of ramelteon does not have a preventive effect on emergence agitation after general anaesthesia in children undergoing tonsillectomy.

DOI： 10.1038/s41598-020-79078-4

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BACKGROUND: It is presently unclear whether the hemodynamic response to intubation is less marked with indirect laryngoscopy using the GlideScope (GlideScope) than with direct laryngoscopy using the Macintosh laryngoscope. Thus, the aim of this study was to determine whether using the GlideScope lowers the hemodynamic response to tracheal intubation more than using the Macintosh laryngoscope. METHODS: We performed a comprehensive literature search of electronic databases for clinical trials comparing hemodynamic response to tracheal intubation. The primary aim was to determine whether the heart rate (HR) and mean blood pressure (MBP) 60 s after tracheal intubation with the GlideScope were lower than after intubation with the Macintosh laryngoscope. We expressed pooled differences in HR and MBP between the devices as the weighted mean difference with 95% confidence interval and also performed trial sequential analysis (TSA). Second, we examined whether use of the GlideScope resulted in lower post-intubation hemodynamic responses at 120, 180, and 300 s compared with use of the Macintosh laryngoscope. For sensitivity analysis, we used a multivariate random effects model that accounted for within-study correlation of the longitudinal data. RESULTS: The literature search identified 13 articles. HR and MBP at 60 seconds post-intubation was not significantly lower with the GlideScope than with the Macintosh (HR vs MBP: weighted mean difference = 0.22 vs 2.56; 95% confidence interval -3.43 to 3.88 vs -0.82 to 5.93; P = .90 vs 0.14; I = 77% vs 63%: Cochran Q, 52.7 vs 27.2). Use of the GlideScope was not associated with a significantly lower HR or MBP at 120, 180, or 300 s post-intubation. TSA indicated that the total sample size was over the futility boundary for HR and MBP. Sensitivity analysis indicated no significant association between use of the GlideScope and a lower HR or MBP at any measurement point. CONCLUSIONS: Compared with the Macintosh laryngoscope, the GlideScope did not lower the hemodynamic response after tracheal intubation. Sensitivity analysis results supported this finding, and the results of TSA suggest that the total sample size exceeded the TSA monitoring boundary for HR and MBP.

DOI： 10.1097/MD.0000000000023345

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PURPOSE: We performed a retrospective cohort study to evaluate whether intraoperative low tidal volume ventilation reduces the incidence of acute kidney injury (AKI) after cardiovascular surgery. MATERIALS AND METHODS: Records of patients who underwent cardiovascular surgery were reviewed. The primary outcome was AKI diagnosed by changes in serum creatinine values. Intraoperative mean tidal volume relative to predicted body weight (PBW) was calculated. The effects of intraoperative mean tidal volumes on AKI incidence were evaluated. RESULTS: Of 338 examined patients, 105 developed AKI. Among patients who received mean tidal volumes of ≤7, >7 to ≤8, >8 to ≤9, and > 9 mL/kg PBW, the AKI incidence was 12.8% (95% confidence interval [CI]: 6.0-25.1%), 29.9% (95% CI: 22.6-38.4%), 38.7% (95% CI: 30.0-48.2), and 34.5% (95% CI: 23.6-47.3%), respectively. Inverse probability of treatment weighting analysis demonstrated that AKI risk was significantly lower in patients who received ≤7 mL/kg PBW than in those who received >7 mL/kg PBW (odds ratio: 0.14, 95% CI: 0.04-0.46, p = .001). CONCLUSIONS: This study suggests that intraoperative low tidal volume ventilation during cardiovascular surgery is associated with a decreased incidence of postoperative AKI. Lowering tidal volume might be a simple strategy for reducing AKI incidence after cardiovascular surgery.

DOI： 10.1016/j.jcrc.2019.12.020

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BACKGROUND: Appropriate pain management is essential to improve the postoperative recovery after total hip arthroplasty (THA). Various case reports have indicated that anterior quadratus lumborum block (QLB) provides effective postoperative analgesia in lower limb surgeries. However, few randomized controlled trials have confirmed the efficacy of anterior QLB for lower limb surgeries. The aim of this single-center, double-blind, randomized controlled trial is to confirm the efficacy of anterior QLB for postoperative recovery after THA. METHODS: The participants will be randomly assigned to either the anterior QLB or placebo groups, using a set of random numbers for the allocation sequence. Only pharmacists will be aware of the allocations; other investigators will be blinded until study completion. After induction of general anesthesia, anterior QLB will be performed by using 0.25% levobupivacaine or normal saline. Fentanyl will be administered according to blood pressure change during the surgery. The primary outcome will be the quality of recovery 40 score (QoR-40). Secondary outcomes will include the visual analog scale score of pain intensity at rest and movement, intraoperative and postoperative doses of fentanyl, and incidence of postoperative nausea and vomiting. Statistical analysis will be performed by using the Student's t test, Mann-Whitney U test, and Fisher's exact test as appropriate. A P value of less than 0.05 will be considered statistically significant. DISCUSSION: The results of our study will reveal whether anterior QLB is effective for postoperative recovery after THA. TRIAL REGISTRATION: UMIN Clinical Trials Registry, UMIN000032255. Registered on 15 April 2018.

DOI： 10.1186/s13063-020-4090-0

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While low-risk patients who undergo elective surgery can tolerate low hematocrit levels, the benefits of higher hematocrit levels might outweigh the risk of transfusion in high-risk patients. Therefore, this study aimed to evaluate the effects of perioperative hematocrit levels on mortality in patients requiring prolonged mechanical ventilation (PMV) after a cardiovascular surgery. This single-center retrospective cohort study was conducted on 172 patients who underwent cardiovascular surgery with cardiopulmonary bypass or off-pump coronary artery bypass grafting and required PMV for ≥72 hours in the intensive care unit (ICU) from 2008 to 2012 at the Yokohama City University Medical Center in Yokohama, Japan. Patients were classified according to hematocrit levels on ICU admission: high (≥30%) and low (<30%) groups. Of 172 patients, 86 were included to each of the low-hematocrit and high-hematocrit groups, with median hematocrit levels (first to third quartiles) of 27.4% (25.4%-28.7%) and 33.0% (31.3%-35.5%), respectively. The difference in survival rates was significant between the two groups using the log-rank test (HR 0.55, 95% CI 0.32 to 0.95, p=0.033). Cox regression analysis revealed that ≥30% increase in hematocrit levels on ICU admission was significantly associated with decreased long-term mortality (HR 0.40, 95% CI 0.20 to 0.80, p=0.0095). Lower hematocrit levels on ICU admission was a risk factor for increased long-term mortality, and higher hematocrit levels might outweigh the risk of transfusion in patients requiring PMV after a cardiovascular surgery.

DOI： 10.1136/jim-2019-001122

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BACKGROUND: Intravenous lidocaine in adults undergoing general anesthesia has been shown to reduce the incidence of postoperative nausea and vomiting (PONV). However, the anti-postoperative vomiting (POV) effect of lidocaine in pediatric patients remains unclear. We conducted a systematic review and meta-analysis with Trial Sequential Analysis to evaluate the effect of intravenous lidocaine on prevention of POV/PONV. METHODS: Six databases including trial registration sites were searched. Randomized clinical trials evaluating the incidence of POV/PONV after intravenous lidocaine compared with control were included. The primary outcome was the incidence of POV within 24 hours after general anesthesia. The incidence of POV was combined as a risk ratio with 95% confidence interval using a random-effect model. We used the I2 to assess heterogeneity. We evaluated the quality of trials using the Cochrane methodology, and we assessed quality of evidence using the Grading of Recommendation Assessment, Development, and Evaluation approach. We also assessed adverse events. RESULTS AND DISCUSSION: Six trials with 849 patients were included, of whom 433 received intravenous lidocaine. Three trials evaluated the incidence of POV, and 3 evaluated the incidence of PONV. The overall incidence of POV within 24 hours after anesthesia was 45.9% in the lidocaine group and 63.4% in the control group (risk ratio, 0.73; 95% confidence interval, 0.53-1.00; I2 = 32%; p = 0.05). The incidence of PONV within 24 hours after anesthesia was 3.73% in the lidocaine group and 4.87% in the control group (RR, 0.76; 95% CI, 0.36-1.59; I2 = 0%; p = 0.47). The quality of evidence was downgraded to "very low" due to the study designs, inconsistency, imprecision, and possible publication bias. CONCLUSION: Our meta-analysis suggests that intravenous lidocaine infusion may reduce the incidence of POV, however, the evidence quality was "very low." Further trials with a low risk of bias are necessary.

DOI： 10.1371/journal.pone.0227904

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Objectives: Serological tests for COVID-19 have been instrumental in studying the epidemiology of the disease. However, the performance of the currently available tests is plagued by the problem of variability. We have developed a high-throughput serological test capable of simultaneously detecting total immunoglobulins (Ig) and immunoglobulin G (IgG) against nucleocapsid protein (NP) and spike protein (SP) and report its performance in detecting COVID-19 in clinical samples. Methods: We designed and prepared reagents for measuring NP-IgG, NP-Total Ig, SP-IgG, and SP-Total Ig (using N-terminally truncated NP (ΔN-NP) or receptor-binding domain (RBD) antigen) dedicated automated chemiluminescent enzyme immunoassay analyzer AIA-CL1200. After determining the basal thresholds based on 17 sera obtained from confirmed COVID-19 patients and 600 negative sera, the clinical validity of the assay was evaluated using independent 202 positive samples and 1,000 negative samples from healthy donors. Results: All of the four test parameters showed 100% specificity individually (1,000/1,000; 95%CI, 99.63-100). The sensitivity of the assay increased proportionally to the elapsed time from symptoms onset, and all the tests achieved 100% sensitivity (153/153; 95%CI, 97.63-100) after 13 days from symptoms onset. NP-Total Ig was the earliest to attain maximal sensitivity among the other antibodies tested. Conclusion: Our newly developed serological testing exhibited 100% sensitivity and specificity after 13 days from symptoms onset. Hence, it could be used as a reliable method for accurate detection of COVID-19 patients and to evaluate seroprevalence and possibly for surrogate assessment of herd immunity.

DOI： 10.3389/fmicb.2020.628281

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BACKGROUND: It is reported that postoperative nausea and vomiting, common general anesthesia complications, may be prevented by perioperative intravenous dextrose administration, but with controversial clinical effectiveness. OBJECTIVE: To evaluate perioperative intravenous dextrose for preventing postoperative nausea and vomiting through a systematic review and meta-analysis of randomized controlled trials with trial sequential analysis. DATA SOURCES: MEDLINE, the Cochrane Central Register of Controlled Trials, Embase, Web of Science, clinicaltrials.gov, and the University Hospital Medical Information Network Clinical Trials Registry were searched from inception until 22 June 2019. ELIGIBILITY CRITERIA: Trials investigating intravenous dextrose effects vs. placebos on postoperative nausea and vomiting in patients who underwent general anesthesia. RESULTS: Eleven trials (1,250 patients) were included. All participants were ASA1-2. The nine trials included laparoscopic surgeries, and 92.2% of the participants were women. The timing of dextrose infusion was before, during, and after surgery in three, five, and three trials, respectively. Our results revealed intravenous dextrose administration significantly reduced postoperative nausea, but not vomiting, during early and late postoperative periods (risk ratio [95% confidence interval], early nausea: 0.76 [0.59-0.99], late nausea: 0.65 [0.48-0.89]; early vomiting: 1.00 [0.81-1.25], late vomiting: 0.96 [0.43-2.16]). Evidence quality was downgraded to low because the trial sequential analysis indicated more trials are needed for firm conclusions. CONCLUSIONS: Compared with placebos, perioperative intravenous dextrose administration may decrease postoperative nausea but not vomiting. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry (registration number: UMIN000030901).

DOI： 10.1371/journal.pone.0231958

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BACKGROUND: Clinical trials regarding the antishivering effect of perioperative magnesium have produced inconsistent results. We conducted a systematic review and meta-analysis with Trial Sequential Analysis to evaluate the effect of perioperative magnesium on prevention of shivering. METHODS: We searched PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, and 2 registry sites for randomized clinical trials that compared the administration of magnesium to a placebo or no treatment in patients undergoing surgeries. The primary outcome of this meta-analysis was the incidence of shivering. The incidence of shivering was combined as a risk ratio with 95% CI using a random-effect model. The effect of the route of administration was evaluated in a subgroup analysis, and Trial Sequential Analysis with a risk of type 1 error of 5% and power of 90% was performed. The quality of each included trial was evaluated, and the quality of evidence was assessed using the Grading of Recommendation Assessment, Development, and Evaluation approach. We also assessed adverse events. RESULTS: Sixty-four trials and 4303 patients (2300 and 2003 patients in magnesium and control groups, respectively) were included. The overall incidence of shivering was 9.9% in the magnesium group and 23.0% in the control group (risk ratio, 0.42; 95% CI, 0.33-0.52). Subgroup analysis revealed that the incidence of shivering was lower with IV (risk ratio, 0.29; 95% CI, 0.29-0.54; Grading of Recommendation Assessment, Development, and Evaluation, moderate), epidural (risk ratio, 0.24; 95% CI, 0.13-0.43; Grading of Recommendation Assessment, Development, and Evaluation, low), and intrathecal administration (risk ratio, 0.64; 95% CI, 0.43-0.96; Grading of Recommendation Assessment, Development, and Evaluation, moderate). Only trials with low risk of bias were included for Trial Sequential Analysis. The Z-cumulative curve for IV magnesium crossed the Trial Sequential Analysis monitoring boundary for benefit even though only 34.9% of the target sample size had been reached. The Z-cumulative curve for epidural or intrathecal administration did not cross the Trial Sequential Analysis monitoring boundary for benefit. No increase in adverse events was reported. CONCLUSIONS: Perioperative IV administration of magnesium effectively reduced shivering and Trial Sequential Analysis suggested that no more trials are required to confirm that IV magnesium effectively reduces shivering.

DOI： 10.1213/ANE.0000000000004024

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Language：Japanese   Publisher：真興交易(株)医書出版部  

【目的】がん患者の入院前待機時期の抑うつ状態は、術後抑うつ状態の危険因子となるか否かを探索することを目的とする。【方法】全身麻酔の手術を受ける初発がん患者を対象とし、入院前待機時期と術後3日目に自記式質問紙調査を行った。抑うつ状態の評価はHospital Anxiety and Depression Scaleを用いた。入院前待機時期と術後3日目の抑うつ状態の関連をロジスティック回帰分析で解析した。【結果】対象者は88名。入院前待機時期に抑うつ状態の者が術後3日目に抑うつ状態となるオッズ比は13.04(95%CI3.90〜43.53)であった。【考察】入院前待機時期の抑うつ状態は、術後抑うつ状態の危険因子であると考えられた。入院前待機時期に術後抑うつ状態に対する予防的介入が行える可能性がある。(著者抄録)

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DOI： 10.1016/j.ajem.2018.12.018

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Supraglottic airway devices are commonly used in general anaesthesia in children. The AuraGain is a newly developed disposable second-generation supraglottic airway device with an inflatable cuff and a gastric port. OBJECTIVE: To confirm our hypothesis that the oropharyngeal leak pressure (OLP) of the AuraGain would be noninferior to that of the i-gel in paediatric patients. DESIGN: A single-blinded, randomised, noninferiority, clinical trial. SETTING: Single-centre trial from January to March 2017. PATIENTS: One hundred paediatric patients (American Society of Anesthesiologists' physical status 1 to 3), aged up to 12 years old, and body weight of 5 to 30 kg requiring a supraglottic airway for elective surgery with an expected surgery time of less than 2 h under general anaesthesia. INTERVENTION: The patients were randomised to allocation to the AuraGain group or the i-gel group. The device size (1.5 to 2.5) used in each group was based on the manufacturer's recommendation. MAIN OUTCOME MEASURES: The primary outcome measure was OLP immediately after insertion, with a predefined noninferiority margin of 3 cmH2O. RESULTS: The OLP immediately after insertion was lower for the AuraGain than for the i-gel (17.1 vs. 23.0 cmH2O; mean difference: -5.9 cmH2O; 95% confidence interval: -8.5 to -3.3 cmH2O; P = 0.98 and <0.001 for noninferiority and superiority, respectively). The first-attempt success rate (AuraGain, 96% vs. i-gel, 90%; P = 0.44) was comparable between the devices. The incidence of blood staining was lower (AuraGain, 6% vs. i-gel, 0%; P = 0.012) and time to insertion was shorter (AuraGain 21.3 vs. i-gel, 17.1 s; P < 0.001) for the i-gel compared with the AuraGain. CONCLUSION: Our noninferiority hypothesis was not adopted. The OLP of the i-gel may be higher than that of the AuraGain, but this superiority hypothesis should be investigated in future trials. The i-gel demonstrated a shorter time to successful placement and lower incidence of blood staining than the AuraGain. TRIAL REGISTRATION: University Hospital Medical Information Network identifier, UMIN000024222.

DOI： 10.1097/EJA.0000000000000987

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The strongest genetic risk factor of Behçet's disease (BD) is HLA-B*51. Our group previously reported that HLA-A*26 is independently associated with the risk of the onset of BD apart from HLA-B*51. Here, we re-evaluated the association between HLA-A*26 and BD in the Japanese population. We also performed a comprehensive literature search and meta-analyzed the extracted published data concerning the relationship between HLA-A*26 and BD to estimate the odds ratio (OR) of HLA-A*26 to BD. In this study, we genotyped 611 Japanese BD patients and 2,955 unrelated ethnically matched healthy controls. Genotyping results showed that the phenotype frequency of HLA-A*26 was higher in BD patients than in controls (OR = 2.12, 95% CI: 1.75-2.56). Furthermore, within the HLA-B*51-negative populations, the phenotype frequency of HLA-A*26 was significantly higher in BD patients than in controls (OR = 3.10, 95% CI: 2.43-3.95). Results obtained from meta-analysis combined with our data showed that the modified OR of HLA-A*26 became 1.80 (95% CI:1.58-2.06), whereas within the HLA-B*51-negative population, the modified OR became 4.02 (95% CI: 2.29-7.05). A subgroup analysis arranged by the geographical regions showed HLA-A*26 is in fact associated with the onset of BD in Northeast Asia (OR = 2.11, 95% CI: 1.75-2.56), but not in the Middle East or in Europe.

DOI： 10.1038/s41598-019-40824-y

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Bilateral quadratus lumborum blockade (QLB) using ultrasound guidance has been introduced as an abdominal truncal block to improve postoperative analgesia and quality of recovery (QoR) after abdominal surgery, but efficacy remains controversial. The primary aim of this study was to evaluate the efficacy of posterior QLB on the postoperative QoR, and secondarily to evaluate postoperative pain after gynaecological laparoscopic surgery (LS). This study was a single-centre randomized controlled trial. QLB group patients underwent bilateral posterior quadratus lumborum injections with 25-30 mL of 0.25% levobupivacaine after induction of general anaesthesia; the control group underwent no block. Both groups were administered fentanyl-based intravenous patient-controlled analgesia postoperatively. The postoperative QoR was measured using the Quality of Recovery 40 (QoR-40) questionnaire score; postoperative pain was evaluated using the visual analogue scale (VAS) and the cumulative postoperative fentanyl dose. Thirty-one and 29 patients were randomised to the QLB and control groups, respectively. The intraoperative remifentanil dosage was significantly less in the QLB group. The median (interquartile range) for the QoR-40 score was not different between the groups: 154 (133-168) in the QLB group and 158 (144-172) in the control group. There were no statistically significant differences in secondary outcome variables. Single-shot QLB did not improve the QoR or postoperative pain in patients managed by multimodal analgesia after gynaecological LS.

DOI： 10.1177/0310057X19838765

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DOI： 10.1213/ANE.0000000000004024

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BACKGROUND: ClearSight is a noninvasive arterial blood pressure monitor, but it remains unknown whether it is affected by the state of perfusion to the fingers. We investigated whether the lower perfusion index (PI) measured with a pulse oximeter, which reflects finger perfusion, would affect the agreement between arterial pressures measured with ClearSight versus those obtained with an arterial catheter. METHODS: Paired arterial pressure data (ClearSight and arterial catheter-based pressures) and PI values were prospectively obtained from 30 patients undergoing major abdominal surgery. The primary outcome was standard deviation (SD) of the bias (precision) of blood pressure between ClearSight and arterial catheter. The ratio of the adjusted SD of the bias between PI≤1 and PI>1 was calculated using the linear mixed-effects model. The secondary outcomes were the bias and the limits of agreement (LOA) between the two devices (repeated measures Bland-Altman analysis). RESULTS: We analyzed 6312 paired data points. The adjusted SD of bias in PI ≤1 compared with those in PI >1 was 1.4-fold (95% confidence interval: 1.3- to 1.4-fold) for systolic arterial pressure, 1.5-fold (95% confidence interval: 1.3- to 1.6-fold) for diastolic arterial pressure, and 1.3-fold (95% confidence interval: 1.2- to 1.5-fold) for mean arterial pressure. The bias (LOA) were as follows: systolic arterial pressure in the PI ≤1 and PI >1 groups, -3.5 (-35.4 to 28.4) mmHg and 2.2 (-19.9 to 24.3) mmHg, respectively; diastolic arterial pressure in the PI ≤1 and PI >1 groups, 13.1 (-5.1 to 31.3) mmHg and 9.0, (-2.6 to 20.6) mmHg, respectively; and mean arterial pressure in the PI ≤1 and PI >1 groups, 8.7 (-11.3 to 28.7) mmHg and 7.6 (-6.2 to 21.3) mmHg, respectively. CONCLUSIONS: PI ≤1 was associated with a large SD of the bias between the devices. The PI value could be a real-time indicator of ClearSight precision.

DOI： 10.1371/journal.pone.0219511

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STUDY OBJECTIVE: The C-MAC laryngoscope (C-MAC) is a videolaryngoscope that uses a modified Macintosh blade. Although several anecdotal reports exist, it remains unclear whether the C-MAC is superior to the Macintosh laryngoscope for tracheal intubation in the adult population. DESIGN: Systematic review, meta-analysis. SETTING: Operating room, intensive care unit. MEASUREMENTS: For inclusion in our analysis, studies had to be prospective randomised trials which compared the C-MAC with the Macintosh laryngoscope for tracheal intubation in the adult population. Data on success rates, intubation time, glottic visualisation and incidence of external laryngeal manipulations (ELM) during tracheal intubation were extracted from the identified studies. In subgroup analysis, we separated those parameters to assess the influence of the airway condition (normal or difficult) and laryngoscopists (novice or experienced). We conducted a trial sequential analysis (TSA). MAIN RESULTS: Sixteen articles with 18 trials met the inclusion criteria. The C-MAC provided better glottic visualisation compared to the Macintosh (RR, 1.08; 95% CI, 1.03-1.14). TSA corrected the CI to 1.01-1.19; thus, total sample size reached the required information size (RIS). Success rates and intubation time did not differ significantly between the laryngoscopes. TSA showed that total sample size reached the RIS for success rates. The TSA Z curve surpassed the futility boundary. The C-MAC required less ELM compared to the Macintosh (RR, 0.83; 95% CI, 0.72-0.96). TSA corrected the CI to 0.67-1.03; 52.3% of the RIS was achieved. In difficult airways, the C-MAC showed superior success rates, glottic visualisation, and less ELM compared to the Macintosh. Among experienced laryngoscopists, the C-MAC offered better glottic visualisation with less ELM than the Macintosh. CONCLUSIONS: The C-MAC provided better glottic visualisation and less ELM (GRADE: Very Low or Moderate), with improved success rates, glottic visualisation, and less ELM in difficult airways.

DOI： 10.1016/j.jclinane.2018.06.007

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BACKGROUND: Fentanyl and remifentanil are widely used opioids in surgery, but it has not been evaluated whether the choice of opioids during surgery affects the patients' postoperative quality of recovery. Accordingly, we aim to compare postoperative recovery of fentanyl-based anesthesia with remifentanil-based anesthesia after laparoscopic surgery using the QoR 40 questionnaire (QoR-40). METHODS: The study was prospective, randomized, patient and investigator-blinded, controlled, clinical trial. Seventy patients undergoing laparoscopic or retroperitoneoscopic renal or ureteral surgery were recruited and randomized to either fentanyl or remifentanil based anesthesia groups. The primary outcome was the global QoR-40 at 24 h after surgery. RESULTS: The global median (interquartile range) QoR-40 score was 160 (138-177) in the fentanyl group (n = 32) and 140 (127-166) in the remifentanil group (n = 31). Physical comfort and physical independence, the two out of the five dimensions of the QoR-40, demonstrated significantly high scores in the fentanyl group (P = 0.047 and P = 0.032, respectively). CONCLUSION: Although the global QoR is higher in the fentanyl group by 20 points compared with remifentanil group, no significant differences revealed between the groups. Further studies with large numbers of subjects of the same gender are needed. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN),  UMIN000010464 . Registered 10 April 2013.

DOI： 10.1186/s12871-018-0547-z

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STUDY OBJECTIVE: To investigate whether Airtraq® attenuate the hemodynamic responses to tracheal intubation using single-lumen tubes in adults as compared with the Macintosh laryngoscope. DESIGN: Meta-analysis. SETTING: Operating room. MEASUREMENTS: The primary outcome of this meta-analysis was to determine whether laryngoscopy using the Airtraq® reduced hemodynamic responses-heart rate (HR) and mean blood pressure (MBP)-at 60 s (s) after tracheal intubation compared to laryngoscopy with the Macintosh laryngoscope. Pooled differences in these hemodynamic responses between the two devices were expressed as weighted mean difference with 95% confidence intervals. We then conducted trial sequential analysis (TSA). The secondary outcome was to investigate whether the Airtraq® reduce the hemodynamic response at 120 s, 180 s, and 300 s after tracheal intubation compared to the Macintosh laryngoscope. We also conducted sensitivity analysis of the hemodynamic responses to tracheal intubation with the laryngoscopes using a multivariate random effects model accounting for within-study correlation of the longitudinal data. MAIN RESULTS: From electronic databases, we selected 11 randomized controlled trials for studies that enrolled subjects satisfying our inclusion criteria. Compared with the Macintosh laryngoscope, the Airtraq® significantly reduced both HR and MBP at 60 s after tracheal intubation. In secondary outcome, the Airtraq® significantly reduced both HR and MBP at all measurement points, excluding HR at 300 s after tracheal intubation. TSA showed that total sample size reached the required information size for both HR and MBP. The sensitivity analysis revealed that the Airtraq® reduced both HR and MBP at all measurement points, excluding HR at 300 s after tracheal intubation. CONCLUSIONS: The Airtraq® attenuates the hemodynamic response at 60 s after tracheal intubation compared with the Macintosh laryngoscope. (GRADE: Low) These results were supported by the sensitivity analysis. TSA suggested that the total sample size was exceeded TSA monitoring boundary both HR and MBP.

DOI： 10.1016/j.jclinane.2018.03.022

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STUDY OBJECTIVE: The McGrath laryngoscope is a novel self-contained videolaryngoscope with a single-use blade. There are several anecdotal reports that the McGrath is superior to the Macintosh laryngoscope for tracheal intubation. However this remains controversial. DESIGN: Meta-analysis and systematic review. SETTING: Operating room or intensive care unit. MEASUREMENTS: A comprehensive literature search was conducted to identify clinical trials that met our inclusion criteria. To qualify, studies had to be prospective randomized trials comparing tracheal intubation between the McGrath and the Macintosh in an adult population. We extracted data on success rate, glottic visualization during intubation, and intubation time from the studies identified. In subgroup analysis, we assessed the influence on each of these parameters which included airway condition (normal or difficult) and operator (novice or experienced). We then conducted a trial sequential analysis (TSA). MAIN RESULTS: Fourteen articles met our inclusion criteria. The McGrath offered better glottic visualization than the Macintosh (risk ratio, 1.34; 95% confidence interval (CI), 1.25-1.45). However, the McGrath required longer intubation time (mean difference, 10.1s; CI, 2.74-17.5) and demonstrated similar success rate of tracheal intubation (risk ratio, 1.00; CI, 0.95-1.05) compared to the Macintosh. TSA showed that total sample size reached the required information size (RIS) in glottic visualization and success rate. However, only 15.1% of the RIS was achieved in intubation time. In the subgroup analysis for airway condition and operator experience level, there were no subgroup differences in both glottic visualization and intubation time. CONCLUSIONS: Our meta-analysis suggests that the McGrath is superior to the Macintosh in terms of glottic visualization (GRADE: moderate). However, it significantly extends intubation time (GRADE: very low) and its success rate (GRADE: very low) for tracheal intubation is not excellent. TSA suggests that further studies are necessary to confirm the results of intubation time.

DOI： 10.1016/j.jclinane.2017.12.030

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PURPOSE: Recently, pediatric ambulatory surgery has become common. However, for some of these patients, unplanned admission or prolonged hospital stay is also necessary, which can increase the mental burden on these patients. The aim of this study was to identify the predictors of the incidence of increased time spent in hospitals associated with pediatric ambulatory surgery. METHODS: Data were obtained from the medical and anesthetic records of 1087 consecutive patients aged < 18 years who underwent ambulatory surgery under general anesthesia. We defined the incidence of increased time spent in a hospital as a composite outcome of unplanned admission and prolonged hospital stay. Multivariate logistic regression analysis was used to examine the associations between the incidence of increased time spent in a hospital and 14 parameters including patient characteristics, anesthesia, and operative factors. RESULTS: Multivariate analysis identified American Society of Anesthesiologist Physical Status (ASA-PS), type of regional block, intraoperative fluid volume, and type of surgery as predictors for the incidence of increased time spent in a hospital. Specifically, caudal block compared to no regional block [odds ratio (OR) (95% confidence interval (CI)) = 0.44 (0.22-0.90)]; increasing intraoperative fluid volume [OR (95% CI) = 0.71 (0.55-0.92) in every increment of 5 ml/kg/h); and ear, nose, and throat (ENT) and urology surgery compared to other types of surgery [OR (95% CI) = 0.13 (0.03-0.64), and 3.93 (1.99-7.77), respectively] were identified as strong predictors. CONCLUSIONS: This study found that the incidence of increased time spent in a hospital in pediatric ambulatory surgery was affected by the type of regional block, intraoperative fluid volume, type of surgery. Potentially modifiable factors, such as intraoperative fluid volume or type of regional block, should be further investigated in future prospective studies.

DOI： 10.1007/s00540-017-2437-9

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BACKGROUND: Emergence agitation (EA) is a frequent phenomenon in children recovering from general anaesthesia and increases the risk of self-injury. Previously, our group reported that stimulating the heart 7 (HT7) acupuncture point bilaterally using two neuromuscular transmission monitoring devices (NTMs) decreased the incidence of EA. However, bilateral stimulation is a barrier to clinical use because two NTMs are needed for one patient. OBJECTIVE: The objective of this study was to examine the efficacy of unilateral electrical stimulation of HT7 using an NTM to prevent EA in children. DESIGN: Prospective, double-blinded, randomized clinical trial. SETTING: Kanagawa Children's Medical Centre, Yokohama, Japan. PATIENTS: One hundred children (ages 18-96 months) with ASA-PS I or II, who were scheduled to undergo inguinal hernia repair or orchiopexy under sevoflurane anaesthesia. INTERVENTION: Patients were randomly assigned to one of the following two groups: (1) HT7 group: unilateral (right side) stimulation of the HT7 acupuncture point using a single-twitch electrical stimulus (1 Hz, 50 mA) throughout the surgery, and (2) control group: electrodes alone were attached to the HT7 point on the right side; an electrical stimulus was not applied. MAIN OUTCOME MEASURES: The primary outcome was the incidence of EA evaluated using the pediatric anaesthesia emergence delirium (PAED) scale. The secondary outcomes were the incidence of EA evaluated using Aono's scale, the severity of EA, PACU stay duration, and postoperative pain. RESULTS: There was no statistical difference between the incidence of EA in the HT7 and the control group (28.0% and 24.0%, respectively; P > 0.99). The risk ratio was 1.17 (95% confidence interval: 0.60-2.27). CONCLUSIONS: We observed that there was no effect of unilateral single-twitch electrical stimulation to the HT7 on the incidence of EA, contrary to the findings with bilateral HT7 stimulation.

DOI： 10.1371/journal.pone.0204533

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BACKGROUND: Magnesium has been investigated as an adjuvant for neuraxial anesthesia, but the effect of caudal magnesium on postoperative pain is inconsistent. The aim of this systematic review and meta-analysis was to evaluate the analgesic effect of caudal magnesium. METHODS: We searched six databases, including trial registration sites. Randomized clinical trials reporting the effect of caudal magnesium on postoperative pain after general anesthesia were eligible. The risk ratio for use of rescue analgesics after surgery was combined using a random-effects model. We also assessed adverse events. The I2 statistic was used to assess heterogeneity. We assessed risk of bias with Cochrane domains. We controlled type I and II errors due to sparse data and repetitive testing with Trial Sequential Analysis. We assessed the quality of evidence with GRADE. RESULTS: Four randomized controlled trials (247 patients) evaluated the need for rescue analgesics. In all four trials, 50 mg of magnesium was administered with caudal ropivacaine. The results suggested that the need for rescue analgesia was reduced significantly by caudal magnesium administration (risk ratio 0.45; 95% confidence interval 0.24-0.86). There was considerable heterogeneity as indicated by an I2 value of 62.5%. The Trial Sequential Analysis-adjusted confidence interval was 0.04-5.55, indicating that further trials are required. The quality of evidence was very low. The rate of adverse events was comparable between treatment groups. CONCLUSION: Caudal magnesium may reduce the need for rescue analgesia after surgery, but further randomized clinical trials with a low risk of bias and a low risk of random errors are necessary to assess the effect of caudal magnesium on postoperative pain and adverse events. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry UMIN000025344.

DOI： 10.1371/journal.pone.0190354

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Authorship：Corresponding author   Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

BACKGROUND: Caudal anesthesia has been used for postoperative pain control in pediatric surgical patients, but the duration of the analgesic effect is occasionally unsatisfactory. Intravenous steroids have been shown to be effective for postsurgical pain management after certain surgeries. The aim of this meta-analysis with trial sequential analysis (TSA) was to evaluate the analgesic effect of steroids in patients administered with caudal anesthesia.
METHODS: This study was a systematic review and meta-analysis. A search of published literature was conducted in the MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials databases and in trial registration sites. Randomized controlled trials that compared intravenous steroids with a placebo in pediatric patients who had received caudal anesthesia for surgery were included in the study. The primary outcomes from the present metaanalysis were the analgesic duration and the number of patients who required rescue analgesics. The analgesic duration and incidence of rescue use were summarized using mean difference or risk ratio with a 97.5% confidence interval (CI), respectively. If the 97.5% CI of the mean difference or risk ratio included a value of 0 or 1, respectively, we considered the difference not to be significant. We used the random effects model to combine the results. Heterogeneity was quantified with the I-2 statistic. The quality of the trials was evaluated using the Cochrane methodology. Moreover, a TSA with a risk of type 1 error of 2.5% and power of 90% was performed. We established the minimum clinically meaningful difference of analgesic duration as 3 hours. The target sample size for meta-analysis was also calculated in the TSA. We also assessed adverse events.
RESULTS: Six trials with 424 patients were included; 211 patients received intravenous steroids. All trials compared dexamethasone of at least 0.5 mg/kg dose with a placebo. Dexamethasone prolonged the duration of caudal analgesia (mean difference, 244 minutes; 97.5% CI, 188-300). Heterogeneity was considerable with an I-2 value of 94.8%. Quality of evidence was very low. The TSA suggested that only 17.0% of the target sample size had been reached, but the cumulative Z score crossed the trial sequential monitoring boundary to indicate a benefit. Rescue use was reported in 4 studies with 260 patients. Rescue use was not significantly reduced in the dexamethasone group (risk ratio, 0.53; 97.5% CI, 0.09-3.30; I-2, 98.7%). No increase in adverse events was reported.
CONCLUSIONS: Intravenous dexamethasone prolongs the analgesic duration of caudal anesthesia. Trials to investigate the effectiveness of a lower dose of the dexamethasone in prolonging analgesic effects would be of interest. Further trials with a low risk of bias are necessary.

DOI： 10.1213/ANE.0000000000002453

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Authorship：Lead author,　Corresponding author   Language：English   Publisher：WILEY  

We conducted both conventional pairwise and Bayesian network meta-analyses to compare the clinical properties of supraglottic airway devices in children. We searched six databases for randomised clinical trials. Our primary end-points were oropharyngeal leak pressure, risk of insertion failure at first attempt, and blood staining risk. The risk of device failure, defined as the abandonment of the supraglottic airway device and replacement with a tracheal tube or another device, was also analysed. Sixty-five randomised clinical trials with 5823 participants were identified, involving 16 types of supraglottic airway device. Network meta-analysis showed that the i-gel, Cobra perilaryngeal airway and Proseal laryngeal mask airway (LMA((R))-Proseal) showed statistically significant differences in oropharyngeal leak pressure compared with the LMA((R))-Classic, with mean differences (95% credible interval, CrI) of 3.6 (1.9-5.8), 4.6 (1.7-7.6) and 3.4 (2.0-4.8) cmH(2)O, respectively. The i-gel was the only device that significantly reduced the risk of blood staining of the device compared with the LMA-Classic, with an odds ratio (95%CrI) of 0.46 (0.22-0.90). The risk (95%CI) of device failure with the LMA-Classic, LMA((R))-Unique and LMA-Proseal was 0.36% (0.14-0.92%), 0.49% (0.13-1.8%) and 0.50% (0.23-1.1%), respectively, whereas the risk (95%CI) of the i-gel and PRO-Breathe was higher, at 3.4% (2.5-4.7%) and 6.0% (2.8-12.5%), respectively. The risk, expressed as odds ratio (95%CrI), of insertion failure at first attempt, was higher in patients weighing &lt; 10 kg at 5.1 (1.6-20.1). We conclude that the LMA-Proseal may be the best supraglottic airway device for children as it has a high oropharyngeal leak pressure and a low risk of insertion. Although the i-gel has a high oropharyngeal leak pressure and low risk of blood staining of the device, the risk of device failure should be evaluated before its routine use can be recommended.

DOI： 10.1111/anae.13970

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Background
Postoperative nausea and vomiting is a distressing complication of surgery, and 5-HT3 receptor antagonists are often prescribed to prevent it. Ondansetron is the agent typically administered to prevent postoperative nausea and vomiting. Although ramosetron has a longer duration of action than ondansetron, it remains unclear whether ramosetron is the more effective medication. We performed an updated meta-analysis on the comparative efficacy of ramosetron and ondansetron in preventing postoperative nausea and vomiting.
Methods
We searched six databases for all trials that randomly assigned patients to ramosetron or ondansetron groups. The primary outcome was postoperative nausea or vomiting in the early, late, and next-day periods. The secondary outcomes were side effects of the medications. We used the random-effects model to combine the results. Trial sequential analyses were performed to correct for repetitive testing in the updated meta-analysis.
Results
Twenty-seven randomized controlled trials with 3,811 patients were included in the meta-analysis. The combined results of ramosetron vs. ondansetron efficacy in preventing postoperative nausea and vomiting were as follows: Risk ratio [95% confidence interval] = 0.82 [0.69-0.98] for early postoperative nausea, 0.76 [0.65-0.89] for late postoperative nausea, 0.69 [0.57-0.84] for next-day postoperative nausea, 0.78 [0.63-0.98] for early postoperative vomiting, 0.57 [0.45-0.72] for late postoperative vomiting, and 0.61 [0.43-0.86] for next-day postoperative vomiting. Dizziness was significantly lower in ramosetron groups than in ondansetron groups (risk ratio [95% confidence interval] = 0.81 [0.66-0.98]). Trial sequential analysis revealed that the results for late postoperative nausea, late postoperative vomiting, and next-day postoperative nausea were conclusive.
Conclusions
Ramosetron is more effective in preventing late postoperative nausea, late postoperative vomiting, and next-day postoperative nausea than ondansetron. The incidence of dizziness may be lower in patients receiving ramosetron than in patients receiving ondansetron.

DOI： 10.1371/journal.pone.0186006

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Language：English   Publisher：ELSEVIER SCIENCE INC  

Study Objective: To evaluate the efficacy of intravenous nitroglycerin (TNG) in preventing intraoperative myocardial ischemia (MI) under general anesthesia. Moreover, we analyzed the hemodynamic changes in heart rate (HR), mean blood pressure (MBP), and pulmonary capillary wedge pressure (PCWP) associated with TNG administration both before and after the induction of anesthesia.
Design: Meta-analysis.
Setting: Operating room, cardiac surgery or non-cardiac surgery, all surgeries were elective measurements. We performed a computerized search of articles on PubMed, Scopus, and the Cochrane Central Register of Controlled Trials. Meta-analysis was performed using Review Manager. The data from the individual trials were combined using a random-effects model to calculate either the pooled relative risk (RR) or the weighted mean difference (WMD) with 95% confidence interval (CI). We conducted trial sequential analysis (TSA). The primary outcome was the incidence of MI and the secondary outcomes were hemodynamic changes (HR, MBP, and PCWP).
Main Results: Using electronic databases, we selected 10 trials with a total of 353 patients for our review. Prophylactic intravenous TNG did not significantly decrease the incidence of MI (RR = 0.61; CI, 0.33 to 1.13; P = 0.12; I-2 = 55). TSA corrected the CI to 0.05 to 7.39 and showed that 9.5% of the required information size was achieved. In terms of hemodynamic changes, intravenous TNG significantly reduced MBP in comparison with the placebo (MBP pre-induction: WMD = - 7.27; 95% CI - 14.2 to - 0.33; P = 0.04; I-2 = 97%; MBP post-induction: WMD = - 5.13; 95% CI -9.17 to - 1.09; P = 0.01; I-2 = 73%).
Conclusions: Our analyses showed that prophylactic intravenous TNG does not reduce the incidence of intraoperative MI. Moreover, TSA suggests that further studies are necessary to confirm the results (GRADE: very low). Prophylactic doses of intravenous TNG significantly reduced the MBP both pre and post anesthesia induction (GRADE: very low). (C) 2017 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.jclinane.2017.03.040

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

BACKGROUND: Emergence agitation (EA) is a common complication in children after general anesthesia. The goal of this 2-phase study was (1) to develop a predictive model (EA risk scale) for the incidence of EA in children receiving sevoflurane anesthesia by performing a retrospective analysis of data from our previous study (phase 1) and (2) to determine the validity of the EA risk scale in a prospective observational cohort study (phase 2).
METHODS: Using data collected from 120 patients in our previous study, logistic regression analysis was used to predict the incidence of EA in phase 1. The optimal combination of the predictors was determined by a stepwise selection procedure using Akaike information criterion. The beta-coefficient for the selected predictors was calculated, and scores for predictors determined. The predictive ability of the EA risk scale was assessed by a receiver operating characteristic (ROC) curve, and the area under the ROC curve (c-index) was calculated with a 95% confidence interval (CI). In phase 2, the validity of the EA risk scale was confirmed using another data set of 100 patients (who underwent minor surgery under general anesthesia). The ROC curve, the c-index, the best cutoff point, and the sensitivity and specificity at the point were calculated. In addition, we calculated the gray zone, which ranges between the two points where sensitivity and specificity, respectively, become 90%.
RESULTS: In phase 1, the final model of the multivariable logistic regression analysis included the following 4 predictors: age (logarithm odds ratios [OR], -0.38; 95% CI, -0.81 to 0.00), Pediatric Anesthesia Behavior score (logarithm OR, 0.65; 95% CI, -0.09 to 1.40), anesthesia time (logarithm OR, 0.60; 95% CI, -0.18 to 1.19), and operative procedure (logarithm OR, 2.53; 95% CI, 1.30-3.75 for strabismus surgery and logarithm OR, 2.71; 95% CI, 0.99-4.45 for tonsillectomy). The EA risk scale included these 4 predictors and ranged from 1 to 23 points. In phase 2, the incidence of EA was 39%. The c-index of phase 1 was 0.84 (95% CI, 0.74-0.94), and the c-index of phase 2 was 0.81 (95% CI, 0.72-0.89). The best cutoff point for the EA risk scale was 11 (sensitivity = 87% and specificity = 61%). The gray zone ranged from 10 to 13 points, and included 38% of patients.
CONCLUSIONS: We developed and validated an EA risk scale for children receiving sevoflurane anesthesia. In our validation cohort, this scale has excellent predictive performance (c-index &gt; 0.8). The EA risk scale could be used to predict EA in children and adopt a preventive strategy for those at high risk. This score-based preventive approach should be studied prospectively to assess the safety and efficacy of such a strategy.

DOI： 10.1213/ANE.0000000000002126

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It is widely accepted that higher mortality related to weekend admissions basically exists; however, there has been no systematic exploration of whether weekend admissions are associated with higher risk of death in patients on the basis of certain diagnoses, geographic regions, and study subtypes.
A meta-analysis was performed according to the reporting guidelines of the Meta-analysis of Observational Studies in Epidemiology (MOOSE Compliant). Literature search was conducted using electronic databases. Primary outcome was short-term (&lt;= 30-day) mortality. Patients were divided into 7 regions (North America, South America, Europe, Asia, Oceania, Africa, and Antarctica) for subgroup analyses and into 7 categories evaluating 24 major diagnoses. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated with DerSimonian and Laird random-effects models.
Eighty-eight studies including 56,934,649 participants met our inclusion criteria. Overall pooled adjusted and crude OR of weekend to weekday admission for short-term mortality was 1.12 (95% CI, 1.07-1.18; I-2=97%) and 1.16 (95% CI, 1.14-1.19; I-2=97%), respectively. In subgroup analyses, higher risk of death on the weekend was significantly identified in patients living in all five continents (North America, South America, Europe, Asia, and Oceania). However, significant weekend effect was identified only in 15 of 24 diagnostic groups. Patients admitted on the weekend were more likely to die in an emergency situation (crude OR=1.17, 95% CI, 1.12-1.22).
Although weekend admissions were associated with higher risk of death compared with weekday admissions on all five continents, the effect was limited to certain diagnostic groups and admission subtypes. Weekend effect remains highly heterogeneous and limited, suggesting that further well-conducted cohort studies might be informative.

DOI： 10.1097/MD.0000000000006685

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：PUBLIC LIBRARY SCIENCE  

Background
The efficacy of devices for difficult intubation in paediatric patients, especially with a Cormack-Lehane grade 4 view, has yet to be established. We compared intubating parameters among three devices (the Airtraq (R), McGrath (R), and Macintosh laryngoscopes).
Methods
This study is a randomised cross-over trial. Participants were 20 anaesthetists. Each device was tested three times using a paediatric manikin with a Cormack-Lehane grade 4 view. The order to use each device was randomised by a computer-generated random sequence. The primary endpoint was the rate of successful intubation. Secondary endpoints included the time taken to intubate, percentage of glottic opening score, and severity of potential dental trauma.
Results
The successful intubation rates of the Airtraq (R), McGrath (R), and Macintosh laryngoscopes were 100%, 72%, and 45%, respectively. The risk ratio of the success rates of Airtraq (R) compared with McGrath (R) and Macintosh laryngoscopes were 1.40 (95% CI; 1.19-1.64, P &lt; 0.001) and 2.22 (95% CI; 1.68-2.94, P &lt; 0.001), respectively. The modified Cormack-Lehane grade and percentage of the glottic opening score were better for the Airtraq (R) than for the other devices. The dental trauma score was lower for the Airtraq (R) than for the other devices. There were no significant differences in the intubation time among the groups.
Conclusions
The Airtraq (R) had higher success rate, had better visibility, and was associated with less dental trauma than the other devices in a difficult paediatric intubation model with a Cormack-Lehane grade 4 view.

DOI： 10.1371/journal.pone.0171889

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：PUBLIC LIBRARY SCIENCE  

Background
Quality of recovery (QoR) after surgery is a relevant outcome. The early postoperative quality of recovery of a patient can be determined using the QoR-40 questionnaire. The aim of this meta-analysis and Trial Sequential Analysis was to determine if perioperative administration of glucocorticosteroids improved patients' quality of recovery after general anesthesia and if adverse events occurred.
Methods
We searched six databases, including trial registration sites. Randomized clinical trials reporting the efficacy of glucocorticosteroids on quality of recovery evaluated using the QoR-40 after general anesthesia were eligible. The QoR-40 data were combined as the mean difference with confidence intervals using a random-effects model. The I-2 statistic was used to assess heterogeneity. The quality of the trials was evaluated using the Cochrane methodology. Moreover, Trial Sequential Analysis was carried out to prevent the inflation of type 1 errors caused by multiple testing and sparse data. We also assessed adverse events.
Results
Three randomized clinical trials (totaling 301 patients) were analyzed. The results from one published and four unpublished randomized clinical trialswere unavailable. Dexamethasone was investigated in all three trials, and the results suggested that it significantly improved QoR-40 at postoperative day one scores compared with placebo (mean difference [95% confidence interval]: 14.2 points [10.4 to 18.1]; P &lt; 0.001; I-2 = 0%). We could not conduct sensitivity analysis because of the absence of trials with low risk of bias. The Trial Sequential Analysis-adjusted confidence interval was -1.6 to 30.0, indicating that further trials are required. The reporting of adverse events was insufficient.
Conclusions
These findings indicate that perioperative dexamethasone administrationmay improve short-term(i.e., one day) quality of recovery after general anesthesia and surgery. We need more randomized clinical trials with low risk of bias assessing the effects of glucocorticosteroids on quality of life, other outcomes, and adverse events. Updated systematic reviews should then be conducted.

DOI： 10.1371/journal.pone.0162961

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

BACKGROUND Emergence agitation is common in children recovering from general anaesthesia. The prevention of emergence agitation remains an important challenge in the field of paediatric anaesthesia.
OBJECTIVE We aimed to examine the effectiveness of electrically stimulating the heart 7 (HT7) acupuncture site with a peripheral nerve stimulator (PNS) during surgery, for preventing emergence agitation in paediatric patients recovering from general anaesthesia.
DESIGN A double-blind, randomised, controlled, parallel-group trial.
SETTING Kanagawa Children's Medical Centre, Yokohama, Japan.
PATIENTS One hundred and twenty patients aged 18 to 96 months (American Society of Anesthesiologists physical status I or II) undergoing minor elective surgery under general anaesthesia with sevoflurane.
INTERVENTION Patients were randomly assigned to either undergo bilateral stimulation of HT7 with two PNS devices (1 Hz, 50 mA) during surgery (Group HT7) or a control group that did not undergo electrical stimulation of HT7 during surgery.
MAIN OUTCOME MEASURES The primary outcome was the incidence of emergence agitation evaluated in the postanaesthesia care unit (PACU) using the Paediatric Anaesthesia Emergence Delirium scale. The secondary outcomes were the time from operation completion to tracheal extubation, PACU stay duration and postoperative pain scores.
RESULTS The incidence of emergence agitation was significantly lower in the HT7 group compared with the control group (31.7 vs. 56.7%, respectively; P = 0.010). The risk ratio was 0.56 (95% confidence interval 0.36 to 0.86) and the number needed to treat was 4 (95% confidence interval 3 to 13). There were no statistically significant differences between groups in time from operation completion to tracheal extubation, PACU stay duration or postoperative pain.
CONCLUSION Bilateral electrical stimulation of HT7 using two PNS devices significantly decreases the incidence of emergence agitation.

DOI： 10.1097/EJA.0000000000000379

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：PUBLIC LIBRARY SCIENCE  

Background
Hypertension often occurs after tracheal intubation using a Macintosh laryngoscope and may lead to rare but serious complications. The Macintosh laryngoscope may increase the incidence of hypertension because it requires forced alignment of the oral and pharyngeal axes in order to view the glottis. In contrast, the McGRATH MAC video laryngoscope does not require this manipulation. The objective of this study was to evaluate the incidence of hypertension after tracheal intubation using a McGRATH laryngoscope compared with a Macintosh laryngoscope.
Methods
Data of 360 consecutive patients who underwent general anesthesia with tracheal intubation by Macintosh laryngoscope or McGRATH video laryngoscope were obtained retrospectively. A total of 16 variables including patient characteristics, anesthetic drug used, and intubation techniques were extracted as potential factors affecting the incidence of hypertension after intubation. The incidence of hypertension after tracheal intubation was defined as an increase in systolic blood pressure (SBP) &gt; 20% of values immediately before intubation. Propensity scoring with inverse probability weighting was used to calculate the odds ratio for the incidence of hypertension after intubation with a McGRATH video laryngoscope as the primary outcome. The mean difference in SBP change between the two laryngoscopes was also calculated.
Results
A McGRATH laryngoscope was used in 68 of 360 patients (18%). The numbers of patients who increase in systolic blood pressure of more than 20% was 189 patients (53%). The odds ratio for the use of a McGRATH laryngoscope was 0.43 (95% confidence interval (CI), 0.19-0.96; P = 0.04). The mean difference in SBP change between the two laryngoscopes was -8.6 mmHg ( 95% CI, -17.4 to 0.2; P = 0.06).
Conclusions
The use of a McGRATH laryngoscope may reduce the incidence of hypertension after tracheal intubation compared to the Macintosh laryngoscope.

DOI： 10.1371/journal.pone.0155566

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BACKGROUND Emergence agitation is a common phenomenon in children recovering from general anaesthesia. An emergence agitation reaction increases the risk of injuring the surgical repair, the patient and the caregivers.
OBJECTIVE The objective of this study is to examine the efficacy of melatonin premedication in emergence agitation prevention.
DESIGN A systematic review and meta-analysis of randomised controlled trials (RCTs) with trial sequential analysis (TSA) and meta-regression analysis.
DATA SOURCES We searched MEDLINE, the Cochrane Central Register of Controlled Trials, Embase, Web of Science, clinicaltrials.gov and UMIN Clinical Trials Registry up to 4 April 2014.
ELIGIBILITY CRITERIA RCTs reporting effects of melatonin on the incidence of emergence agitation in children who underwent general anaesthesia were included.
RESULTS Four studies (358 participants) were analysed. A conventional random-effects meta-analysis showed that compared with placebo, melatonin premedication may be effective in emergence agitation prevention [risk ratio 0.31, 95% confidence interval (CI) 0.16 to 0.60; I-2 = 0%]. However, TSA corrected the 95% CI to 0.07 to 1.47 and showed that 22.5% of the required information size (RIS) was achieved. The effect of melatonin compared with that of midazolam was not statistically significant (risk ratio 0.48, 95% CI 0.15 to 1.52) with significant heterogeneity (I-2 = 36.8%). TSA-adjusted 95% CI could not be calculated because of the small information size (4% of RIS). Metaregression showed that, compared with midazolam, melatonin dose was significantly correlated with the effect (P = 0.024). The risk ratios (95% CI) of low and high-dose melatonin were 1.02 (0.39 to 2.65) and 0.22 (0.08 to 0.58), respectively. There was no effect of melatonin compared with dexmedetomidine (risk ratio 1.0, 95% CI 0.15 to 6.55). TSA-adjusted 95% CI could not be calculated (0.9% of RIS).
CONCLUSION Compared with placebo, melatonin premedication may be effective in preventing emergence agitation in children (GRADE: low). This TSA suggests that further studies are required to confirm the results. Compared with midazolam, high-dose melatonin might have a significant effect in preventing emergence agitation (GRADE: very low). The study protocol was registered in the UMIN Clinical Trials Registry (registration number: UMIN000011841).

DOI： 10.1097/EJA.0000000000000323

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BACKGROUND: Patients with acute respiratory distress syndrome receiving mechanical ventilation show inhomogeneous lung aeration. Atelectasis during uneven mechanical ventilation leads to alveolar hypoxia and could therefore result in lung inflammation and injury. We aimed to elucidate whether and how atelectasis causes alveolar hypoxia-induced inflammation during uneven mechanical ventilation in an open-chest differential-ventilation rat model. METHODS: We first investigated inflammatory and histological changes in the bilateral lungs of unilaterally ventilated rats, in which the right lung was atelectatic and the left lung was ventilated with high tidal volume (HTV). In the next series, we investigated the effects of normal tidal volume (NTV) ventilation of the right lungs with 60 % O2 or 100 % N2 during HTV ventilation of the left lungs. Then, proinflammatory cytokine secretions were quantified from murine lung epithelial (MLE15) and murine alveolar macrophage (MH-S) cells cultured under a hypoxic condition (5 % O2) mimicking atelectasis. Further, activities of nuclear factor (NF)-κB and hypoxia-inducible factor (HIF)-1 were assessed in the nonventilated atelectatic lung and MLE15 cells cultured under the hypoxic condition. Finally, effects of NF-κB inhibition and HIF-1α knockdown on the cytokine secretions from MLE15 cells cultured under the hypoxic condition were assessed. RESULTS: The nonventilated atelectatic lungs showed inflammatory responses and minimal histological changes comparable to those of the HTV-ventilated lungs. NTV ventilation with 60 % O2 attenuated the increase in chemokine (C-X-C motif) ligand (CXCL)-1 secretion and neutrophil accumulation observed in the atelectatic lungs, but that with 100 % N2 did not. MLE15 cells cultured with tumor necrosis factor (TNF)-α under the hypoxic condition showed increased CXCL-1 secretion. NF-κB and HIF-1α were activated in the nonventilated atelectatic lungs and MLE15 cells cultured under the hypoxic condition. NF-κB inhibition abolished the hypoxia-induced increase in CXCL-1 secretion from MLE15 cells, while HIF-1α knockdown augmented it. CONCLUSIONS: Atelectasis causes alveolar hypoxia-induced inflammatory responses including NF-κB-dependent CXCL-1 secretion from lung epithelial cells. HIF-1 activation in lung epithelial cells is an anti-inflammatory response to alveolar hypoxia in atelectatic lungs.

DOI： 10.1186/s40635-015-0056-z

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PUBLIC LIBRARY SCIENCE  

Background
Numerous studies have demonstrated the beneficial effects of preoperative administration of oral carbohydrate (CHO) or oral rehydration solution (ORS). However, the effects of preoperative CHO or ORS on postoperative quality of recovery after anesthesia remain unclear. Consequently, the purpose of the current study was to evaluate the effect of preoperative CHO or ORS on patient recovery, using the Quality of Recovery 40 questionnaire (QoR-40).
Methods
This prospective, randomized, controlled clinical trial included American Society of Anesthesiologists (ASA) physical status 1 and 2 adult patients, who were scheduled to undergo a surgical procedure of body surface. Subjects were randomized to one of the three groups: 1) preoperative CHO group, 2) preoperative ORS group, and 3) control group. The primary outcome was the global QoR-40 administered 24 h after surgery. Intraoperative use of vasopressor, intraoperative body temperature changes, and postoperative nausea and vomiting (PONV) were also evaluated.
Results
We studied 134 subjects. The median [interquartile range (IQR)] global QoR-40 scores 24 h after the surgery were 187 [177-197], 186 [171-200], and 184 [171-198] for the CHO, ORS, and control groups, respectively (p = 0.916). No significant differences existed between the groups regarding intraoperative vasopressor use during the surgery (p = 0.475).
Conclusions
Results of the current study indicated that the preoperative administration of either CHO or ORS did not improve the quality of recovery in patients undergoing minimally invasive body surface surgery.

DOI： 10.1371/journal.pone.0133309

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Spinal anaesthesia for caesarean section induces hypotension, which may cause severe adverse effects. Our goal was to determine whether hypotension could be predicted by pulse oximetry parameters, such as the perfusion index and pleth variability index, heart rate, ratio of low-frequency to high-frequency components of heart rate variability, and entropy of heart rate variability, measured before the induction of anaesthesia. The predictive value of these parameters for detecting hypotension was assessed using logistic regression and the grey zone approach in 81 parturients. Logistic regression revealed heart rate to be the only independent predictor (OR 1.06; 95% CI 1.01-1.13; p=0.032). The grey zone for heart rate was in the range of 71-89bpm, and 60.5% of parturients were in the grey zone. Pre-anaesthetic heart rate, but not other parameters derived from pulse oximetry or heart rate variability, may be a prognostic factor for hypotension associated with spinal anaesthesia.

DOI： 10.1111/anae.12992

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：DAEDALUS ENTERPRISES INC  

BACKGROUND: For early detection of respiratory and hemodynamic changes during anesthesia, continuous end-tidal carbon dioxide concentration (P-ETCO2) is monitored by capnometry. However, the accuracy of CO2 monitoring during spontaneous breathing in extubated patients remains undetermined. Therefore, we aimed to compare P-ETCO2 measured by capnometry using an oxygen mask with a carbon dioxide sampling port (capnometry-type oxygen mask) and P-CO2 in extubated subjects who had undergone abdominal surgery. Furthermore, we investigated whether spontaneous deep breathing affected dissociation between P-aCO2 and P-ETCO2. METHODS: Adult post-abdominal surgery subjects admitted to the ICU were enrolled in this study. After extubation, oxygen was supplied at 6 L/min using the capnometry-type oxygen mask. After 30 min of oxygen supply, P-aCO2 blood gas analysis was performed, and P-ETCO2 was measured under resting and deep-breathing conditions. For both resting and deep-breathing conditions, the correlation between P-aCO2 and P-ETCO2 was analyzed. Furthermore, bias, precision, and limits of agreement were calculated using the Bland-Altman method. RESULTS: Twenty-five subjects (15 men, 10 women) with a mean age of 62 y (interquartile range of 57-76 y) and body mass index of 20-24 kg/m(2) were studied. The correlation (r) between P-aCO2 and P-ETCO2 under resting and deep-breathing conditions was 0.50 and 0.56, respectively. Compared with P-aCO2, the bias and limits of agreement were -12.6 (-20.6 to -4.6) for resting P-ETCO2 and -9.1 (-16.0 to -2.1) for deep-breathing P-ETCO2. The association between P-aCO2 and deep-breathing P-ETCO2 was significantly smaller compared with resting P-ETCO2 (P = .002). CONCLUSIONS: It is possible to measure the P-ETCO2 under varying breathing conditions with the capnometry-type oxygen mask in subjects receiving oxygen supplementation after extubation following upper abdominal surgery to determine whether they are properly ventilating. (ClinicalTrials.gov registration UMIN000011925.) (C) 2015 Daedalus Enterprises

DOI： 10.4187/respcare.03557

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Authorship：Lead author,　Corresponding author   Language：English   Publisher：WILEY-BLACKWELL  

The purpose of this meta-analysis was to determine the efficacy of lidocaine in preventing laryngospasm during general anaesthesia in children. An electronic search of six databases was conducted. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were adhered to. We included randomised controlled trials reporting the effects of intravenous and/or topical lidocaine on the incidence of laryngospasm during general anaesthesia. Nine studies including 787 patients were analysed. The combined results demonstrated that lidocaine is effective in preventing laryngospasm (risk ratio (RR) 0.39, 95% CI 0.24-0.66; I-2=0). Subgroup analysis revealed that both intravenous lidocaine (RR 0.34, 95% CI 0.14-0.82) and topical lidocaine (RR 0.42, 95% CI 0.22-0.80) lidocaine are effective in preventing laryngospasm. The results were not affected by studies with a high risk of bias. We conclude that, both topical and intravenous lidocaine are effective for preventing laryngospasm in children.

DOI： 10.1111/anae.12788

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Background: General anesthesia induces long-lasting cognitive and learning deficits. However, the underlying mechanism remains unknown. The GluA1 subunit of AMPAR is a key molecule for learning and synaptic plasticity, which requires trafficking of GluA1-containing AMPARs into the synapse.
Methods: Adult male rats were exposed to 1.8% isoflurane for 2 h and subjected to an inhibitory avoidance task, which is a hippocampus-dependent contextual fear learning paradigm (n = 16 to 39). The in vitro extracellular field potential of hippocampal synapses between the Schaffer collateral and the CA1 was evaluated using a multielectrode recorder (n = 6 per group). GluA1 expression in the synaptoneurosome was assessed using Western blotting (n = 5 to 8). The ubiquitination level of GluA1 was evaluated using immunoprecipitation and Western blotting (n = 7 per group).
Results: Seven days after exposure to 1.8% isoflurane for 2 h (Iso(1.8)), the inhibitory avoidance learning (control vs. Iso(1.8); 294 +/- 34 vs. 138 +/- 28, the mean +/- SEM [%]; P = 0.002) and long-term potentiation (125.7 +/- 6.1 vs. 105.7 +/- 3.3; P &lt; 0.001) were impaired. Iso(1.8) also temporarily increased GluA1 in the synaptoneurosomes (100 +/- 9.7 vs. 138.9 +/- 8.9; P = 0.012) and reduced the GluA1 ubiquitination, a main degradation pathway of GluA1 (100 +/- 8.7 vs. 71.1 +/- 6.1; P = 0.014).
Conclusions: Isoflurane impairs hippocampal learning and modulates synaptic plasticity in the postanesthetic period. Increased GluA1 may reduce synaptic capacity for additional GluA1-containing AMPARs trafficking.

DOI： 10.1097/ALN.0000000000000269

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Background: It has been shown that ?-aminobutyric acid exerts excitatory actions on the immature brain due to the increased expression of Na+-K+-2Cl? cotransporter isoform 1. The authors sought to clarify whether midazolam, a ?-aminobutyric acid-mimetic hypnotic agent, causes neuronal excitation that can be blocked by bumetanide, a selective inhibitor of Na+-K+-2Cl? cotransporter isoform 1. Furthermore, the authors examined whether bumetanide potentiates the sedative effects of midazolam in neonatal rats. Methods: The authors measured the effects of midazolam with or without bumetanide on the cytosolic Ca2+ concentration ([Ca]2+ i) in hippocampal slices (n = 3 in each condition) from rats at postnatal days 4, 7, and 28 (P4, P7, and P28) using fura-2 microfluorometry. Neuronal activity in the hippocampus and thalamus after intraperitoneal administration of midazolam with or without bumetanide was estimated by immunostaining of phosphorylated cyclic adenosine monophosphate-response element-binding protein (n = 12 in each condition). Furthermore, the authors assessed effects of bumetanide on the sedative effect of midazolam by measuring righting reflex latency (n = 6 in each condition). Results: Midazolam significantly increased [Ca]2+ i in the CA3 area at P4 and P7 but not at P28. Bumetanide inhibited midazolam-induced increase in [Ca]2+ i. Midazolam significantly up-regulated phosphorylated cyclic adenosine monophosphate-response element-binding protein expression in a bumetanide-sensitive manner in the hippocampus at P7 but not P28. Bumetanide enhanced the sedative effects of midazolam in P4 and P7 but not P28 rats. Conclusion: These results suggest that ?-aminobutyric acid A receptor-mediated excitation plays an important role in attenuated sedative effects of midazolam in immature rats. © 2013, the American Society of Anesthesiologists.

DOI： 10.1097/ALN.0b013e31829e4b05

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (international conference proceedings)  

Background: Obturator nerve block is performed on patients who undergo transurethral resection of inferolateral bladder tumors to prevent thigh adductor muscle contraction. However, other than the tumor site, we have no criteria to judge whether this block is necessary in all patients. Moreover, it is difficult to predict the efficacy of obturator nerve block before resection. To solve these problems, we have devised a trans-resectoscope stimulation technique that involves delivering several single-twitch electrical stimuli to the inside wall of the bladder via a resectoscope to elicit contraction of the thigh adductor muscle. Methods: Trans-resectoscope stimulation was performed in 51 cases on 45 patients for which urologists had requested obturator nerve block. If no thigh adductor muscle contraction was observed with trans-resectoscope stimulation (i.e., negative result), tumor resection was performed without further investigation. If the result was positive, we performed obturator nerve block or administered a muscle relaxant until the result turned negative. Positive or negative responses to the initial trans-resectoscope stimulation and thigh adductor muscle contraction during subsequent resection were recorded. Results: The initial trans-resectoscope stimulation result was negative in 29 of the 51 cases (57%). In these cases, tumor resection was allowed to proceed, and no thigh adductor muscle contraction occurred (rate of incidence [95% confidence interval]: 0% [0%-5.7%]). In cases with a positive initial trans-resectoscope stimulation result (22/51 or 43%), we performed an obturator nerve block or administered a muscle relaxant after which we once again stimulated to verify the lack of adductor response before proceeding with the resection, and no thigh adductor muscle contraction was observed during resection. Conclusions: Trans-resectoscope stimulation is beneficial not only to predict the need to block the contraction of the thigh adductor during tumor resection but also to avoid unnecessary obturator nerve block. © 2013 International Anesthesia Research Society.

DOI： 10.1213/ANE.0b013e3182a07063

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

BACKGROUND: Ramosetron has been shown to have a very strong effect for preventing postoperative nausea and vomiting (PONV) in previous meta-analyses. However, these previous meta-analyses included a number of studies by Fujii et al. which have now been proven to have been fabricated. In the present meta-analysis, we reevaluated the effectiveness of ramosetron in preventing PONV after excluding Fujii et al.'s randomized controlled trials.
METHODS: We searched MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and Web of Science. All double-blind randomized controlled trials that tested the efficacy of ramosetron compared with a placebo or other drugs as a control in the prophylaxis of PONV were considered to be eligible. The first postoperative 24 hours were divided into early (0-6 hours) and late (6-24 hours) time periods, and we collected these data separately.
RESULTS: A total of 1372 patients were included in the final analysis. Compared with a placebo, ramosetron reduced the incidence of early postoperative nausea (PON) (relative risk [RR] [95% confidence interval] 0.59 [0.47-0.73]: number needed to treat [NNT] [95% confidence interval] 6.0 [4.3-9.7]), late PON (RR 0.65 [0.49-0.85]: NNT 7.2 [4.6-16.6]), early postoperative vomiting (POV) (RR 0.48 [0.31-0.74]: NNT 14.8 [8.3-70.4]), and late POV (RR 0.50 [0.35-0.73]: NNT 12.3 [7.1-47.6]). Compared with ondansetron, ramosetron reduces early POV (RR 0.50 [0.28-0.90]: NNT 24.1 [10.7-98.0]) and late POV (RR 0.53 [0.34-0.81]: NNT 27.2 [12.0-102.0]) but not PON.
CONCLUSIONS: Ramosetron has a significant effect for preventing PONV compared with a placebo, but less than that reported in previous analyses. Ramosetron also has statistically significant differences in preventing early and late POV compared with ondansetron, but the clinical significance may be questioned because the NNTs are large.

DOI： 10.1213/ANE.0b013e31829847a1

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General anesthesia is occasionally associated with postoperative complications such as sleep disorder, drowsiness, or mood alterations. Hippocampal acetylcholine (ACh), the extracellular level of which increases during the dark (active) phase and decreases during the light (rest) phase in rats, is thought to be associated with locomotor activity and be crucial for learning and memory. Propofol, an intravenous anesthetic, is known to shift the circadian rhythms of physiological parameters including locomotor activity and body temperature in both rodents and humans, while the effects of volatile anesthetics on the circadian rhythm largely remain unclear. The present study examined the effects of isoflurane anesthesia on the diurnal changes in hippocampal ACh release and locomotor activity in rats. Rats were divided into three groups: a light-phase anesthesia group (LA group), a dark-phase anesthesia group (DA group), and a control group. They were exposed to a 12-h light/12-h dark environment and anesthetized with 1.4% isoflurane for 4. h during the middle of the light phase (LA group) and dark phase (DA group). Simultaneous measurement of hippocampal ACh by microdialysis and locomotor activity were done for 60. h under free-moving conditions. Hippocampal ACh release and locomotor activity showed a clear circadian rhythm. In the DA group, but not in the LA group, the diurnal variation in ACh release was significantly disturbed and a more than 2-h phase-advance in locomotor activity was observed. There was a significant correlation between hippocampal ACh release and locomotor activity, and isoflurane anesthesia disrupted it even after anesthesia was discontinued. This study revealed that the levels and circadian rhythms of hippocampal ACh release and locomotor activity were more sensitive to isoflurane anesthesia when it was administered during the active phase. Our findings suggest that anesthesia exerts differential effects on the regulation of circadian rhythms depending on the circadian phase. © 2013 IBRO.

DOI： 10.1016/j.neuroscience.2013.01.062

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BACKGROUND: An unintended bolus is delivered by the syringe pump if intravenous line occlusion is released in an inappropriate manner.
OBJECTIVE: The aim of this study was to measure the amount of flushed fluid when an occlusion is inappropriately released and to assess the effect of different syringe pump settings (flow rate, alarm setting, size of syringe and syringe pump model) on the flushed amount.
METHODS: After the stopcock was closed, infusions were started with different model syringe pumps (Terufusion (R) TE312 and TE332S), different syringe sizes or at different alarm settings. After the occlusion alarm sounded, the occlusion was released and the amount of fluid emerging from the stopcock was measured.
RESULTS: The bolus was significantly lower when the alarm was set at a low-pressure setting. The bolus was significantly lower with a 10-ml than a 50-ml syringe. A significant difference was seen only when a 50-ml syringe was used (TE312: 1.99 +/- 0.16 ml vs. TE332S: 0.674 +/- 0.116 ml, alarm High, p &lt; 0.001).
CONCLUSION: To minimize the amount of accidentally injected medication, a smaller syringe size and a low alarm setting are important. Using a syringe pump capable of reducing the inadvertently administered bolus may be helpful.

DOI： 10.3233/THC-130754

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Background: Surgery with general anesthesia disturbs circadian rhythms, which may lead to postoperative sleep disorders and delirium in patients. However, it is unclear how circadian rhythms are affected by different anesthetics administered at different times during the rest-activity cycle. We hypothesized that pentobarbital (an agonist at the γ-aminobutyric acid A receptors) and ketamine (an antagonist at the N-methyl-D-aspartate receptors) would have differential effects on circadian rhythms, and these effects would also be influenced by the time of their administration (the active versus resting phase). Methods: Rats were divided into 4 groups according to the anesthetic administered (pentobarbital or ketamine) and the timing of intraperitoneal administration (active/night phase or resting/day phase). Using online pineal microdialysis, we analyzed pineal melatonin secretion and locomotor activity rhythms in rats under a light/dark (12/12-hour) cycle for 5 days after anesthesia and microdialysis catheter implantation. The data were analyzed for rhythmicity by cosinor analysis. Results: Ketamine administered during the resting phase produced 65- and 153-minute phase advances, respectively, in melatonin secretion and locomotor activity rhythms on the first day after anesthesia. In contrast, ketamine administered during the active phase produced 43- and 235-minute phase delays. Pentobarbital had no effect on the phase of either melatonin secretion or locomotor activity, irrespective of the timing of administration. When administered during the active phase, both anesthetics decreased the amplitude of melatonin secretion on the day after anesthesia
when administered during the resting phase, however, neither anesthetic affected the amplitude. The amplitude of locomotor activity decreased in all animals for 3 days after anesthesia. Conclusion: Ketamine has opposite phase-shifting effects on circadian rhythms according to the time of administration, whereas pentobarbital has no effect. Furthermore, both anesthetics decrease the postoperative amplitude of pineal melatonin secretion if administered during the active, but not the resting, phase of the 24-hour rest-activity cycle. Copyright © 2012 International Anesthesia Research Society.

DOI： 10.1213/ANE.0b013e3182632bcb

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Language：English   Publishing type：Rapid communication, short report, research note, etc. (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

DOI： 10.1097/EJA.0000000000000358

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Language：English   Publishing type：Rapid communication, short report, research note, etc. (scientific journal)   Publisher：WILEY-BLACKWELL  

DOI： 10.1111/anae.13229

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Language：English   Publisher：SPRINGER JAPAN KK  

Emanuel syndrome is a rare anomaly associated with multiple systemic malformations. We present two cases involving pediatric patients with Emanuel syndrome. The first patient presented with micrognathia and had patent ductus arteriosus and a single kidney. The patient was difficult to intubate with McGRATH(A (R)) but was successfully intubated with an Airtraq(A (R)) device. The second patient did not present with micrognathia and was not difficult to intubate. A thorough examination of the heart, kidney, and spinal cord is important when planning the anesthetic management of patients with Emanuel syndrome. Moreover, adequate preparation for a difficult airway is essential, and the Airtraq(A (R)) device may be useful for intubating patients with Emanuel syndrome with micrognathia.

DOI： 10.1007/s00540-014-1955-y

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：SPRINGER  

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Language：Japanese   Publisher：日本臨床麻酔学会  

キセノンに麻酔作用があることが1946年に報告されて以来さまざまな研究が行われ,その特性が麻酔薬として理想的であることが判明している.キセノンはすでに欧州では麻酔薬として臨床認可されており,本邦でも臨床認可される可能性はあると考えられる.キセノンは導入・覚醒が早い,鎮痛作用を持つ,術中の循環動態が安定する,脳保護作用を持つ,術後認知機能障害を予防できる可能性がある,といった多数の利点を持っている.しかし一方で,キセノン自体のコストは高く,臨床普及を阻む欠点となっている.本稿ではキセノン麻酔の利点と欠点を概説し,今後の展望についてまとめる.(著者抄録)

DOI： 10.2199/jjsca.33.736

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Language：English   Publishing type：Rapid communication, short report, research note, etc. (scientific journal)   Publisher：WILEY-BLACKWELL  

DOI： 10.1111/pan.12153

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A 50-year-old woman with massive ovarian cancer underwent a tumor resection and lymph node resection. Oxygenation was impaired preoperatively and chest X-ray film and computed tomogram revealed an elevation of the two diaphragms and atelectasis of the lower parts of the lungs. Induction of anesthesia was uneventful. During the surgery, oxygenation was improved after laparotomy but deteriorated again about 90 minutes after the tumor resection. Just before the termination of the surgery, we found bubbly sputum coming out from the tracheal tube. We had her chest X-ray taken and found bilateral consolidation of the lower parts of the lungs with air-bronchogram and loss of diaphragm profiles. The diagnosis of RPE was made and she was, transferred to ICU without extubation. Evacuation of pneumothorax or pleural effusion is the most common cause of RPE
but, removal of the intraabdominal mass would provide a good chance for RPE. Although, slow expansion of the collapsed lungs to prevent RPE is recommended, this consideration may not always be warranted.

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