Damage-associated molecular patterns as a mechanism of sevoflurane-induced neuroinflammation in neonatal rodents.

Background: General anesthesia is inevitable for pediatric patients undergoing surgery, though volatile anesthetic agents may cause neuroinflammation and neurodevelopmental impairment; however, the underlying pathophysiology remains unclear. We aimed to investigate the neuroinflammation mechanism in developing rat brains associated with sevoflurane exposure time, by identifying the specific damage-associated molecular patterns (DAMPs) pathway and evaluating the effects of non-steroidal anti-inflammatory drugs (NSAIDs) in alleviating neuroinflammation. Methods: A three-step experiment was conducted to investigate neuroinflammation induced by sevoflurane. First, the exposure time required for sevoflurane to cause neuroinflammation was determined. Next, the specific pathways of DAMPs involved in neuroinflammation by sevoflurane were identified. Finally, the effects of NSAIDs on sevoflurane-induced neuroinflammation were investigated. The expression of various molecules in the rat brain were assessed using immunohistochemistry (IHC), immunofluorescence (IF), quantitative real-time polymerase chain reaction (PCR), western blot analysis, and enzyme-linked immunosorbent assay (ELISA). Results: In total, 112 rats (aged 7 d) were used, of which six rats expired during the experiment (mortality rate, 5.3%). Expression of CD68, HMGB-1, galectin-3, TLR4, TLR9, and phosphorylated NF-κB was significantly increased upon 6 h of sevoflurane exposure. Conversely, transcriptional levels of TNF-α and IL-6 significantly increased and IFN-γ significantly decreased after 6 h of sevoflurane exposure. Co-administration of NSAIDs with sevoflurane anesthesia significantly attenuated TNF-α and IL-6 levels and restored IFN-γ levels. Conclusions: In conclusion, 6 h of sevoflurane exposure induces neuroinflammation through the DAMPs pathway, HMGB-1, and galectin-3. Co-administration of ibuprofen reduced sevoflurane-induced neuroinflammation.

Intravenous dexamethasone does not prolong the duration of pudendal nerve block in infants and children undergoing hypospadias surgery: A randomized clinical trial.

BACKGROUND: The administration of intravenous dexamethasone increases the duration of neuraxial block and improves the quality of analgesia. However, little is known about these effects of dexamethasone on peripheral nerve blocks in children. AIMS: In this study, we aimed to investigate the benefit of intravenous dexamethasone for enhancing the effect of pudendal block on postoperative analgesia in children who underwent hypospadias surgery. METHODS: In total, 46 children aged 6-36 months who underwent hypospadias surgery were randomly allocated to either a control group (normal saline, group C) or dexamethasone group (0.5 mg/kg, group D). Pudendal block was performed before the surgery using 0.3 mL/kg of 0.225% ropivacaine on both sides. Parents were instructed to press the patient-controlled analgesia bolus button when their children's pain score was >4 points. The primary outcome measure was the time at which the first patient-controlled analgesia by proxy bolus dose was administered. The secondary outcome measures were pain score, number of patient-controlled analgesia administration by proxy bolus attempts, number of rescue analgesics required, total amount of fentanyl administered, and overall parental satisfaction. RESULTS: The time of first patient-controlled analgesia bolus administration by proxy was not different between the control and dexamethasone groups (5.6 [5.2, 8.8] h versus 6.5 [5.4, 8.1] h, hazard ratio 0.8, 95% confidence intervals 0.43 to 1.47, p = .46). There were no statistically significant differences among the secondary outcomes. CONCLUSIONS: Administration of intravenous dexamethasone did not enhance the duration of pudendal nerve block in infants and children aged 6-36 months who underwent hypospadias surgery.

Effect of analgesia nociception index monitor-based nociception control on perioperative stress responses during laparoscopic surgery in Trendelenburg position: a randomized controlled trial.

Introduction: The analgesia nociception index (ANI) monitor is a nociception monitoring device based on heart rate variability. We aimed to determine the effect of ANI monitor-based intraoperative nociception control on the perioperative stress response during laparoscopic surgery in the Trendelenburg position. Methods: Altogether, 72 female patients who underwent total laparoscopic hysterectomy were randomized to either the control or ANI group. Intraoperative nociception was controlled by remifentanil administration in a conventional manner (based on blood pressure and heart rate) in the control group and by ANI monitoring in the ANI group. Perioperative stress responses were estimated by measuring the levels of serum catecholamines and catabolic stress hormones at three timepoints: after loss of consciousness, at the end of surgery, and 1 h after the end of surgery. Results: The serum cortisol level at the end of surgery was significantly higher in the ANI group than in the control group (p < 0.001), although more remifentanil was administered in the ANI group than in the control group (p < 0.001). Changes in the other estimators' levels were comparable between groups during the perioperative period. The hemodynamic profiles during surgery were also significantly different between the two groups. Phenylephrine use to treat hypotension was more common in the ANI group than in the control group (p = 0.005). However, postoperative clinical outcomes such as pain and nausea/vomiting did not differ between groups. Conclusion: ANI monitor-based nociception control in laparoscopic surgery in the Trendelenburg position did not improve perioperative stress responses, intraoperative opioid consumption, or postoperative clinical outcomes.Clinical trial registration: ClinicalTrials.gov (NCT04343638).

A Novel Propofol Dosing Regimen for Pediatric Sedation during Radiologic Tests.

The dose of propofol for pediatric sedation during radiologic tests has been proposed as an equation of 0.75 + 0.14 × age (months) + 45.82 × body surface area (m2) based on results in a previous study. We compared this equation and the conventional dosing strategy for sedation in children undergoing radiologic tests. An amount of 180 children scheduled for magnetic resonance imaging (MRI) were randomized to experimental and control groups. The initial induction dose of propofol calculated using the equation was administered in the experimental group. In the control group, children received 1 mg/kg of the initial induction dose of propofol. Then, 0.5 mg/kg of the additional dose was followed to induce sedation in both groups. When awake or moving, a rescue injection of 0.5 mg/kg propofol was given. The total induction dose was more significant in the experimental group. The number of injections for induction in the experimental group was lesser. The dose and number of rescue injections in the experimental group were significantly less. The equation for the induction dose of propofol in a previous study could achieve quick induction of sedation and prevent a rescue injection during sedation. However, caution is needed when using the equation.

Effects of positive end-expiratory pressure on pulmonary atelectasis after paediatric laparoscopic surgery as assessed by ultrasound: A randomised controlled study.

INTRODUCTION: Positive end-expiratory pressure (PEEP) following alveolar recruitment manoeuvre (RM) can effectively prevent anaesthesia-induced atelectasis in children. We aimed to evaluate the individual effect of PEEP following RM on atelectasis at the end of laparoscopic surgery in infants and small children. METHODS: Children undergoing laparoscopic inguinal hernia repair aged 5 weeks to 2 years were randomly allocated to either the PEEP or control group. A progressive RM was performed after intubation in all cases. The PEEP group received PEEP of 5 cmH2O until the end of mechanical ventilation, while the control group did not receive any PEEP. Lung ultrasonography was performed to compare the number of atelectatic regions between the two groups after anaesthesia induction, after RM, and at the end of surgery in 12 thoracic regions. RESULTS: Overall, 432 ultrasonographic images were acquired from 36 children. At the end of surgery, the number of atelectatic regions (median [interquartile range]) was significantly lower in the PEEP group compared to the control group (2.0 [1.0-3.0] versus 4.0 [3.0-4.0] out of 12 regions, respectively; p = 0.02). While no difference was observed between the number of atelectatic regions after induction and at the end of surgery in the control group (p = 0.30), a decrease was observed in the PEEP group (3.0 [2.0-4.0] to 2.0 [1.0-3.0], respectively; p = 0.02). CONCLUSION: RM followed by a PEEP of 5 cmH2O can effectively reduce the regions of pulmonary atelectasis at the end of laparoscopic surgery in infants and small children.

Identification for antitumor effects of tramadol in a xenograft mouse model using orthotopic breast cancer cells.

In our previous research showed that tramadol having potential anti-tumor effect was associated with enhancement of oncological prognosis in patients with breast cancer surgery. As these effects have not been confirmed by clinical dose-regulated animal or prospective human studies, we investigated the anti-tumor effect of tramadol in vivo. Female nude mice orthotopically inoculated with luciferase-expressing MCF-7 cells, were randomly divided into the control (saline), tramadol group 1 (1.5 mg kg-1 day-1), tramadol group 2 (3 mg kg-1 day-1), and morphine (0.5 mg kg-1 day-1) (n = 5/group). Bioluminescence signals after D-luciferin injection, tumor size, and tumor weight were compared among groups after 4 weeks. Estrogen receptor (ER), progesterone receptor (PR), and transient receptor potential vanilloid (TRPV)-1 expression, natural killer (NK) cell activity, and serum interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-6 were then examined. Tumour growth was attenuated in tramadol-treated groups (P < 0.05). NK cell activity was significantly decreased only in the morphine treated group not in sham, control, and tramadol groups. The expression levels of ERα, PRα and ß, and TRPV1 were decreased in tramadol group 2 compared with those in the morphine group, but not compared to the control group. Serum levels of IL-6 and TNFα were reduced in both tramadol-treated group 1 and 2 compared to the control group. Overall, clinical dose of tramadol has anti-tumour effects on MCF-7 cell-derived breast cancer in a xenograft mouse model.

The effect of oxygen concentration on atelectasis formation during induction of general anesthesia in children: A prospective randomized controlled trial.

BACKGROUND: In adults, the use of lower oxygen concentration during induction is associated with less atelectasis formation without an increase in incidence of hypoxia. However, it is unknown whether this remains true in the pediatric patients. METHODS: Fifty-four pediatric patients who were scheduled to undergo elective lower abdominal surgery were randomized to one of three oxygenation groups: 100%, 80%, or 60% oxygen (in air). During anesthesia induction, patients were ventilated with sevoflurane in 100%, 80%, or 60% oxygen. Endotracheal intubation and mechanical ventilation were performed. Atelectasis was diagnosed using LUS, which was performed after anesthetic induction and at the end of surgery. RESULTS: We assessed atelectasis after anesthetic induction and at the end of surgery. After anesthetic induction, the number of atelectatic lung regions was significantly different among the three groups (median [IQR], 2.0 [1.0-2.5], 2.0 [1.0-2.8], and 3.0 [2.0-3.0] in the 60%, 80%, and 100% oxygen groups, p = .033) and between the 60% and 100% groups (p = .015), but not between 80% and 100% groups (p = .074). However, no differences in the number of atelectatic lung regions were found among the three groups at the end of surgery (2.0 [1.3-3.8], 3.0 [1.8-3.0], and 4.0 [2.0-4.0] in the 60%, 80%, and 100% oxygen groups; p = .169). CONCLUSION: Lower oxygen concentration during anesthetic induction is associated with less atelectasis formation immediately after anesthetic induction in children. In addition, applying 80% oxygen instead of 100% oxygen is not enough to prevent atelectasis formation, and 60% oxygen should be applied to prevent atelectasis. However, this effect does not last until the end of surgery.

Pulmonary function of healthy Korean children from three independent birth cohorts: Validation of the Global Lung Function Initiative 2012 equation.

BACKGROUND AND OBJECTIVE: Global Lung Function Initiative (GLI) 2012 equations were developed to resolve the age-related disparity in interpreting spirometry results. Local validation of the equation is needed, especially in Northeast Asian children. This study evaluated the GLI equation in Korean children. METHODS: Spirometry indices (FEV1, FVC, FEV1/FVC, and FEF25%-75%) and clinical information were gathered from three population-based birth cohorts. Predicted GLI reference values and z scores of spirometry results were calculated for 1239 healthy children. The mean, standard deviation of z scores were compared with the expected 0 and 1. Probabilities of falling below the lower limit of normal (LLN) (z score: -1.64) were compared with the expected value 5%. GLI z scores were assessed according to low (<-2), normal (≥-2 and ≤2), and high (>2) BMI z score groups. RESULTS: Mean z scores significantly differed from 0 for FEV1/FVC in males (mean [95% confidence interval]: 0.18 [0.08, 0.27]) and forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) in females (-0.23 [-0.31, -0.15] and -0.26 [-0.36, -0.16], respectively). The standard deviation was larger than 1 for all variables in males and FVC and FEV1/FVC in females. The probability of falling below the LLN was significantly larger than 5% for FEV1 (12.13% [9.64, 14.77]), FVC (15.86% [13.06, 18.81]), and forced expiratory flow at 25%-75% of forced vital capacity (FEF25%-75%) (7.31% [5.29, 9.49]) in males and FVC (11.91% [9.40, 14.60]) in females. FEV1 and FVC z scores increased across low to high body mass index (BMI) groups, and FEV1/FVC decreased from low to high BMI groups. CONCLUSION: GLI equations marginally differ from real-world values, which should be considered by pulmonologists in practice or research.

Tracheal intubation with or without a neuromuscular blocking agent for a short surgical procedure in children: Prospective, randomized, double-blind trial.

BACKGROUND: Although a neuromuscular blocking agent during induction of anesthesia is the standard of care in adults, some pediatric anesthesiologists remain concerned about their use for several reasons. Therefore, propofol and short-acting opioids with a moderate concentration of sevoflurane have been used as alternatives to a neuromuscular blocking agent. AIMS: This study compared propofol, alfentanil, and rocuronium to determine the optimal anesthetic agent for intubation conditions as well as emergence in a short pediatric procedure. METHODS: In this prospective, randomized, double-blind study, 114 pediatric patients, aged 1-9 years, were randomly assigned to one of three groups receiving either propofol 2 mg kg-1 (propofol group), alfentanil 14 mcg kg-1 (alfentanil group), or rocuronium 0.3 mg kg-1 (rocuronium group). The primary outcome was intubating conditions, which were evaluated 90 s after test drug administration. Vital signs were recorded during the intubation period. Complications during and after emergence, time to recovery, airway-related complications, and severity of emergence agitation were recorded. RESULTS: Compared with the propofol group (60%), significantly more excellent intubating conditions were observed in the alfentanil group (97%, percent difference -37, 95% confidence interval (CI) -54.4--21.0, p < .001) and the rocuronium group (87%, percent difference -27, 95% CI -46.5--8.2, p = .041). Hemodynamic responses were different between the rocuronium and alfentanil groups, although the incidence of adverse events was not different among the three groups. The emergence duration was only statistically different between the rocuronium group [9.9 ± 3.2 min] and the propofol group [11.7 ± 2.2 min] (difference 95% CI 0.667-3.583, p = .001), while that of the alfentanil group [10.9 ± 2.4 min] was comparable with the other groups. CONCLUSIONS: Both 0.3 mg kg-1 rocuronium and 14 µg kg-1 alfentanil are superior adjuncts for tracheal intubation in children undergoing frenulectomy in comparison with 2 mg kg-1 propofol. Hemodynamic adverse events and recovery profiles were comparable among the three groups.

Quality of Recovery of Patients Who Underwent Curative Pancreatectomy: Comparison of Total Intravenous Anesthesia Versus Inhalation Anesthesia Using the QOR-40 Questionnaire.

BACKGROUND: There has been increasing attention on the subjective recovery of patients undergoing cancer surgery. Total intravenous anesthesia (TIVA) and inhaled anesthesia with volatile anesthetics (INHA) are safe and common anesthetic techniques. Currently, TIVA and INHA have only been compared for less invasive and less complex surgeries. This prospective randomized trial aimed to compare the quality of recovery between TIVA and INHA in patients undergoing pancreatoduodenectomy (PD) or distal pancreatectomy (DP) using the Quality of Recovery (QOR)-40 questionnaire. METHODS: We enrolled 132 patients who were randomly assigned to either the desflurane (DES) (INHA, balanced anesthesia with DES and remifentanil infusion) or TIVA (effect-site target-controlled infusion of propofol and remifentanil) groups and completed the QOR-40 questionnaire postoperatively. RESULTS: The mean global QOR-40 score on postoperative day 3 was significantly higher in the TIVA group than in the DES group. In the PD group, the total QOR-40 score was significantly higher in the TIVA group than in the DES group. Moreover, the TIVA group had significantly higher scores in the physical comfort and psychological support QOR-40 dimensions than the DES group. CONCLUSION: TIVA provides better quality of recovery scores on POD 3 for patients undergoing curative pancreatectomy. CLINICAL TRIAL REGISTRATION NUMBER: NCT03447691.

Optimal positive end-expiratory pressure to prevent anaesthesia-induced atelectasis in infants: A prospective, randomised, double-blind trial.

BACKGROUND: Paediatric patients have a particularly high incidence of anaesthesia-induced atelectasis. Applying positive end-expiratory pressure (PEEP) with an alveolar recruitment manoeuvre has been substantially studied and adopted in adults; however, few studies have been conducted in children. OBJECTIVE: We compared the effects of three levels of PEEP (3, 6 and 9 cmH2O) on anaesthesia-induced atelectasis measured by ultrasound in infants between 6 and 12 months of age who were undergoing general anaesthesia. DESIGN: A prospective, randomised, double-blind trial. SETTING: Department of Anaesthesia, single centre, South Korea, from May 2019 to March 2020. PATIENTS: Children who were 6 to 12 months of age, whose American Society of Anesthesiologists (ASA) physical status was 1 or 2, whose height and weight were within two standard deviations of those of their peers, and who were scheduled for elective urological or general surgery were included in the study. MAIN OUTCOME MEASURES: The primary outcome was the lung ultrasound score at the end of the procedure. The secondary outcomes included dynamic compliance, peak inspiratory pressure, driving pressure, cardiac index, mean arterial pressure and heart rate before and after applying PEEP. RESULTS: The mean lung ultrasound score at the end of operation was 12.8 at PEEP 6 cmH2O and 12.1 at PEEP 9 cmH2O. Both were significantly lower than 18.4 at PEEP 3 cmH2O (P = 0.0002 and 0.00003, respectively). However, there was no significant difference between the scores of PEEP 6 cmH2O and PEEP 9 cmH2O. The Δ cardiac index (the cardiac index after PEEP - the cardiac index at 3 cmH2O of PEEP) was comparable among the three groups. CONCLUSION: To reduce anaesthesia-induced atelectasis measured by ultrasound in healthy infants undergoing low abdominal, genitourinary or superficial regional operations, 6 cmH2O of PEEP was more effective than 3 cmH2O. PEEP of 9 cmH2O was comparable with 6 cmH2O. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03969173.

Effect of upper respiratory infection on anaesthesia induced atelectasis in paediatric patients.

Upper respiratory tract infection (URI) symptoms are known to increase perioperative respiratory adverse events (PRAEs) in children undergoing general anaesthesia. General anaesthesia per se also induces atelectasis, which may worsen with URIs and yield detrimental outcomes. However, the influence of URI symptoms on anaesthesia-induced atelectasis in children has not been investigated. This study aimed to demonstrate whether current URI symptoms induce aggravation of perioperative atelectasis in children. Overall, 270 children aged 6 months to 6 years undergoing surgery were prospectively recruited. URI severity was scored using a questionnaire and the degree of atelectasis was defined by sonographic findings showing juxtapleural consolidation and B-lines. The correlation between severity of URI and degree of atelectasis was analysed by multiple linear regression. Overall, 256 children were finally analysed. Most children had only one or two mild symptoms of URI, which were not associated with the atelectasis score across the entire cohort. However, PRAE occurrences showed significant correspondence with the URI severity (odds ratio 1.36, 95% confidence interval 1.10-1.67, p = 0.004). In conclusion, mild URI symptoms did not exacerbate anaesthesia-induced atelectasis, though the presence and severity of URI were correlated with PRAEs in children.Trial registration: Clinicaltrials.gov (NCT03355547).

Effect of dexmedetomidine on sevoflurane-induced neurodegeneration in neonatal rats.

BACKGROUND: Structural brain abnormalities in newborn animals after prolonged exposure to all routinely used general anaesthetics have raised substantial concerns for similar effects occurring in millions of children undergoing surgeries annually. Combining a general anaesthetic with non-injurious sedatives may provide a safer anaesthetic technique. We tested dexmedetomidine as a mitigating therapy in a sevoflurane dose-sparing approach. METHODS: Neonatal rats were randomised to 6 h of sevoflurane 2.5%, sevoflurane 1% with or without three injections of dexmedetomidine every 2 h (resulting in 2.5, 5, 10, 25, 37.5, or 50 µg kg-1 h-1), or fasting in room air. Heart rate, oxygen saturation, level of hypnosis, and response to pain were measured during exposure. Neuronal cell death was quantified histologically after exposure. RESULTS: Sevoflurane at 2.5% was more injurious than at 1% in the hippocampal cornu ammonis (CA)1 and CA2/3 subfields; ventral posterior and lateral dorsal thalamic nuclei; prefrontal, retrosplenial, and somatosensory cortices; and subiculum. Although sevoflurane 1% did not provide complete anaesthesia, supplementation with dexmedetomidine dose dependently increased depth of anaesthesia and diminished responses to pain. The combination of sevoflurane 1% and dexmedetomidine did not reliably reduce neuronal apoptosis relative to an equianaesthetic dose of sevoflurane 2.5%. CONCLUSIONS: A sub-anaesthetic dose of sevoflurane combined with dexmedetomidine achieved a level of anaesthesia comparable with that of sevoflurane 2.5%. Similar levels of anaesthesia caused comparable programmed cell death in several developing brain regions. Depth of anaesthesia may be an important factor when comparing the neurotoxic effects of different anaesthetic regimens.

Pediatric characteristics and the dose of propofol for sedation during radiological examinations: a retrospective analysis.

OBJECTIVE: The present study aimed to investigate patients' characteristics that can affect the dose of propofol required to sedate children undergoing imaging. METHODS: In this retrospective, observational study, we reviewed medical records of children aged 0 to 18 years who were classified as having American Society of Anesthesiologists status 1 or 2 and they underwent imaging under propofol sedation between January 2011 and August 2016. Collected data included patients' demographics, propofol doses, duration of sedation, and complications. Regression analysis was performed to determine patients' characteristics that may affect the dose of propofol required to induce sedation. RESULTS: A total of 925 patients were included. Simple linear regression showed that the dose of propofol was correlated with age, height, weight, and body surface area. Using the results of multiple linear regression, the following formula was used to estimate the dose of propofol (mg) for sedation: 0.75 + 0.14 × age (months) + 45.82 × body surface area (m2). CONCLUSION: A child's age, height, and body surface area should be considered when deciding the induction dose of propofol. Additionally, the formula that we have proposed can be used to estimate the dose of propofol required to induce sedation in children undergoing imaging.

Correlation of Intraoperative End-Tidal Carbon Dioxide Concentration on Postoperative Hospital Stay in Patients Undergoing Pylorus-Preserving Pancreaticoduodenectomy.

BACKGROUND: Hypocapnia has been traditionally advocated during general anesthesia, even though it may induce deleterious physiological effects that result in unfavorable outcomes in patients. This study investigated the association between intraoperative end-tidal carbon dioxide (EtCO2) and length of hospital stay (LOS) in patients who underwent pylorus-preserving pancreaticoduodenectomy (PPPD). METHODS: The medical records of 759 patients from 2006 to 2015 were reviewed. The patients were divided into two groups based on the mean EtCO2 value during general anesthesia: the hypocapnia group (< 35 mmHg) and the normocapnia group (≥ 35 mmHg). The primary outcome was LOS between the groups. Secondary outcomes included the length of intensive care unit (ICU) stay, postoperative 30-day, 1-year, and 2-year mortality, and perioperative factors associated with LOS. RESULTS: A total of 727 patients were finally analyzed. The median LOS of the hypocapnia group was significantly longer than that of the normocapnia group (22 days vs. 18 days, respectively; p < 0.001). Postoperative mortality did not differ between the groups. Cox regression analysis revealed that hypocapnia was an independent risk factor for longer LOS (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.37-1.89; p < 0.001). Age and postoperative pancreatic fistula were also risk factors for a longer LOS. CONCLUSIONS: It was concluded that low levels of intraoperative EtCO2 during general anesthesia were associated with an increased LOS for patients undergoing PPPD.

Independent risk factors for adverse events associated with propofol-based pediatric sedation performed by anesthesiologists in the radiology suite: a prospective observational study.

This study aimed to identify the types and frequencies of adverse events, as well as the risk factors for respiratory complications related to pediatric sedation. This single-center, prospective, observational study was conducted in a radiology suite at a tertiary university hospital for 2 years. Patients aged under 18 years, who underwent sedation solely by anesthesiologists for computed tomography or magnetic resonance imaging scans, were eligible for inclusion. Univariate and multivariate logistic regression analyses were carried out to identify the risk factors of adverse events, including respiratory complications, related to the propofol-based sedation. We further performed a sensitivity test with 1-to-5 propensity score matching analysis to assess the robustness of our findings. Among 2569 children, 3.9% experienced respiratory problems related to the sedation. After 1-to-5 propensity matching analysis, cardiac and neurologic comorbidities, crying before sedation, a history of snoring or upper respiratory infection, and prolonged duration of sedation were independently associated with the occurrence of adverse respiratory events.Conclusions: Our protocol for pediatric sedation demonstrates a high success rate and low likelihood of fatal complications, but proactive management prior to propofol-based sedation is critical to prevent adverse respiratory events in children. What is Known: • Propofol-based pediatric sedation is associated with adverse events necessarily even though performed by professional anesthesiologists solely. What is New: • Cardiac and neurologic comorbidities, crying before sedation, a history of snoring or upper respiratory infection, and prolonged duration of sedation were independently associated with the occurrence of respiratory adverse events. • Proactive management prior to sedation is critical to preventing adverse respiratory events for pediatrics.

Comparison of Monotherapy Versus Combination of Intravenous Ibuprofen and Propacetamol (Acetaminophen) for Reduction of Postoperative Opioid Administration in Children Undergoing Laparoscopic Hernia Repair: A Double-Blind Randomized Controlled Trial.

BACKGROUND: Extensive efforts have been made toward reducing postoperative opioid use in children. In this study, we assessed whether propacetamol, or a nonsteroidal anti-inflammatory drug (NSAID), or their combination could effectively reduce opioid use in children after laparoscopic inguinal hernia repair. METHODS: This randomized, double-blind clinical trial included 159 children aged 6 months to 6 years. Children were allocated into 1 of the following 3 groups: group I was treated with 10 mg·kg-1 ibuprofen, group P was treated with 30 mg·kg-1 propacetamol, and group I + P was treated with both drugs in their respective concentrations. If the face-legs-activity-crying-consolability (FLACC) score was ≥4 during the postanesthesia care unit stay, 1.0 µg·kg-1 fentanyl was administered as a rescue analgesic. The number of patients who received rescue fentanyl in the postanesthesia care unit was defined as the primary outcome; this was analyzed using the χ2 test. The secondary outcomes included the FLACC and the parents' postoperative pain measure (PPPM) scores until the 24-hour postoperative period. RESULTS: Among the 144 enrolled patients, 28.6% in group I, 66.7% in group P, and 12.8% in group I + P received rescue fentanyl in the postanesthesia care unit (P < .001). The highest FLACC score was lower in group I + P than in either group I or P (P = .007 and P < .001, respectively). Group I + P presented significantly lower PPPM scores than group P at 4 and 12 hours postoperative (P = .03 and .01, respectively). CONCLUSIONS: The use of ibuprofen plus propacetamol immediately following laparoscopic hernia repair surgery in children resulted in the reduced use of an opioid drug compared with the use of propacetamol alone.

Prognostic role of serum high mobility group box 1 concentration in cardiac surgery.

Outcomes of cardiac surgery are influenced by systemic inflammation. High mobility group box 1 (HMGB1), a pivotal inflammatory mediator, plays a potential role as a prognostic biomarker in cardiovascular disease. The aim of this prospective, observational study was to investigate the relationship between serum HMGB1 concentrations and composite of morbidity endpoints in cardiac surgery. Arterial blood samples for HMGB1 measurement were collected from 250 patients after anaesthetic induction (baseline) and 1 h after weaning from cardiopulmonary bypass (post-CPB). The incidence of composite of morbidity endpoints (death, myocardial infarction, stroke, renal failure and prolonged ventilator care) was compared in relation to the tertile distribution of serum HMGB1 concentrations. The incidence of composite of morbidity endpoints was significantly different with respect to the tertile distribution of post-CPB HMGB1 concentrations (p = 0.005) only, and not to the baseline. Multivariable analysis revealed post-CPB HMGB1 concentration (OR, 1.072; p = 0.044), pre-operative creatinine and duration of CPB as independent risk factors of adverse outcome. Accounting for its prominent role in mediating sterile inflammation and its relation to detrimental outcome, HMGB1 measured 1 h after weaning from CPB would serve as a useful biomarker for accurate risk stratification in cardiac surgical patients and may guide tailored anti-inflammatory therapy.

Safety of Donation From Brain-dead Organ Donors With Central Nervous System Tumors: Analysis of Transplantation Outcomes in Korea.

BACKGROUND: This study aims to verify the condition of recipients of solid organs from donors with central nervous system (CNS) tumors and determine the risk of disease transmission due to transplantation. METHODS: Twenty-eight brain-dead organ donors with CNS tumors and 91 recipients who received solid organs from January 1, 2005, to December 31, 2014 in Korea were investigated using the Korean Network of Organ Sharing data. RESULTS: Of the 36 recipients of organs from the 11 donors whose pathological results were not verified, 4 developed the following tumors: renal cell carcinoma, carcinoma in situ of the cervix uteri, B-cell lymphoma, and colon cancer. Among 51 recipients from 17 donors with CNS tumor, no recipient had the same tumor as the donors. Six were classified as high-risk donors according to the World Health Organization classification, and 14 recipients from these donors did not develop tumor after transplantation. The remaining 11 donors were classified as low-risk donors according to the World Health Organization classification but as high-risk donors according to the Malignancy Subcommittee of the Disease Transmission Advisory Committee of the Organ Procurement and Transplantation Network/United Network for Organ Sharing. Of the 37 recipients, 3 had recurring hepatocellular carcinoma with lung and bone metastases, thyroid cancer, and Kaposi's sarcoma after transplantation. CONCLUSIONS: The risk of disease transmission due to organ transplantation from donors with CNS tumors was very low. Thus, organ donation from such donors should be promoted actively to expand the donor range.

Systemic Lidocaine Infusion for Post-Operative Analgesia in Children Undergoing Laparoscopic Inguinal Hernia Repair: A Randomized Double-Blind Controlled Trial.

Systemic lidocaine can provide satisfactory post-operative analgesia in adults. In this study, we assessed whether intravenous lidocaine is effective for post-operative analgesia and recovery in children undergoing laparoscopic inguinal hernia repair. A total of 66 children aged from six months to less than six years were classified in either the lidocaine (L) or control (C) groups. Children in Group L received a lidocaine infusion (a bolus dose of 1 mL kg-1, followed by a 1.5 mg kg-1 h-1 infusion), whereas Group C received the same volume of 0.9% saline. The primary outcome was the number of patients who presented face, legs, activity, crying and consolability (FLACC) scores of four or more, and therefore received rescue analgesia in the post-anesthesia recovery care unit (PACU). Secondary outcomes included the highest FLACC score in the PACU, FLACC, and the parents' postoperative pain measure (PPPM) score at 48 h post-operation, as well as side effects. The number of children who received rescue analgesia in the PACU was 15 (50%) in Group L and 22 (73%) in Group C (p = 0.063). However, the highest FLACC score in PACU was lower in Group L (3.8 ± 2.4) than in Group C (5.3 ± 2.7) (p = 0.029). In conclusion, systemic lidocaine did not reduce the number of children who received rescue analgesia in PACU.