INJEX50 could improve the success rate of local anesthesia for arterial cannulation in the pediatric intensive care unit: A randomized, double-blind, single-center study.

BACKGROUND: Quick arterial cannulation is required in pediatric emergency situation, which require effective local anesthesia to avoid withdrawal movement. However, pediatric local anesthesia could be difficult because of withdrawal movement. Jet injectors, which are needleless and provide local anesthesia quickly, could be helpful for pediatric local anesthesia during arterial cannulation. AIMS: This study aimed to examine whether new jet injector "INJEX50" could improve the success rate of local anesthesia for arterial cannulation in pediatric intensive care unit compared with the current standard of care, infiltration using a 26-gauge needle. METHODS: This study was a randomized, double-blind, single-center study. Participants were infants and young children in the pediatric intensive care unit, who required an arterial line. Local anesthesia was performed with either a 26-gauge needle (group C) or INJEX50 (group I) before arterial cannulation. The primary outcome (success of local anesthesia) was the presence of withdrawal movement at the time of skin puncture for arterial cannulation. The secondary outcomes included rescue sedation during arterial cannulation. Data were analyzed using Fisher's exact test and the Mann-Whitney U-test, with values of p < .05 considered statistically significant. RESULTS: Seventy patients were randomly assigned to groups C and I. The local anesthesia success rate in group I (30/35 [86%]) was significantly higher than that in group C (15/35 [43%], odds ratio, 8.00; 95% confidence interval, 2.51-25.5; p = .0005). In conclusion, INJEX50 could improve success rate of local anesthesia for arterial cannulation in pediatric intensive care unit compared with 26-gauge needle.

Head cooling wrap could suppress the elevation of core temperature after cardiac surgery during forced-air warming in a pediatric intensive care unit: a randomized clinical trial.

PURPOSE: The main aim of the current trial was to explore our hypothesis that cooling head wraps lower the core temperature more effectively than ice packs on the head during forced-air warming after pediatric cardiac surgeries. METHODS: This study was a single-center Randomized Controlled Trial. Participants were children with a weight ≤ 10 kg and hyperthermia during forced-air warming after cardiac surgeries. When the core temperature reached 37.5 °C, ice packs on the head (group C) or a cooling head wrap (group H) were used as cooling devices to decrease the core temperature. The primary outcome was the core temperature. The secondary outcomes were the foot surface temperature and heart rate. We measured all outcomes every 30 min for 240 min after the patient developed hyperthermia. We conducted two-way ANOVA as a pre-planned analysis and also the Bonferroni test as a post hoc analysis. RESULTS: Twenty patients were randomly assigned to groups C and H. The series of core temperatures in group H were significantly lower than those in group C (p < 0.0001), and post hoc analysis showed that there was no significant difference in core temperatures at T0 between the two groups and statistically significant differences in all core temperatures at T30-240 between the two groups. There was no difference between the two groups' surface temperatures and heart rates. CONCLUSIONS: Compared to ice packs on the head, head cooling wraps more effectively suppress core temperature elevation during forced-air warming after pediatric cardiac surgery.

Analysis of the radial and ulnar arteries using ultrasound and a vascular visualization device in children.

BACKGROUND: Radial artery is the preferred site for cannulation. Recently, the ulnar artery was chosen as an alternative in adults. AIMS: We aimed to measure the diameter and depth of the ulnar and radial arteries using ultrasound, and our secondary purpose was to evaluate their anatomical position using a near-infrared transcutaneous illumination device. METHODS: Forty-eight children (age range: 0-144 months) were assigned to the following groups: group Infant (aged <12 months), group Preschool (aged ≤12 to <72 months), and group School (aged ≥72 months). The diameter, depth, and position of the ulnar and radial arteries were compared between groups. RESULTS: There was no significant difference between the diameters of the ulnar and radial arteries. In group Infant, group Preschool, and group School, mean diameters of the ulnar artery were 1.27 ± 0.15 mm, 1.62 ± 0.27 mm, and 2.03 ± 0.28 mm, respectively, and the radial artery were 1.29 ± 0.15 mm, 1.69 ± 0.27 mm, and 2.06 ± 0.29 mm, respectively. The corresponding differences between the diameters of ulnar and radial arteries were -0.02 mm, -0.07 mm, and -0.02 mm [95% CI -0.16 mm to 0.12 mm, -0.25 mm to 0.11 mm, and -0.25 mm to 0.21 mm; p = .776, p = .411, and p = .852]. In groups Preschool and School, the ulnar artery was at the recommended depth of 2-4 mm for arterial cannulation compared with the radial artery. In the Infant, Preschool, and School age groups, the ulnar and radial arteries were at the recommended depth of 2-4 mm for arterial cannulation in 70.0%, 100.0%, 93.8%, and 80.0%, 65.0%, and 50.0% of the cases, respectively. (difference: -10.0%, 35.0%, and 43.8%, 95%; CI -43.4% to 23.4%, 14.1% to 55.9%, and 19.4% to 68.1%, respectively). CONCLUSIONS: The ulnar artery can be considered a promising alternative to the radial artery for facilitating arterial cannulation in children.

Safety of an improved pediatric epidural tunneling technique for catheter shear.

BACKGROUND: Epidural tunneling could help with prolonged catheterization and be effective in preventing infection and dislodgement. However, epidural tunneling techniques carry a risk of catheter shear or needlestick injuries. AIMS: This study aimed to examine the safety of our epidural tunneling technique in terms of catheter shear. METHODS: This study was designed as a double-blinded, single-crossover, in vitro study. Each of the operators performed two techniques to create a subcutaneous tunnel. We compared outcomes between the control tunneling technique (group C) and our improved technique (group I). Microscopic findings of catheter shear were assessed as the primary outcome. Secondary outcomes included the tension and displacement required to break the epidural catheter and the frequency of catheter breakage due to catheter shear. Data were analyzed using the Fisher's exact test and Mann-Whitney U test. A p-value of <.05 was considered statistically significant. RESULTS: Ten catheters were assessed in each group. The frequency of catheter shear was 10% in group I and 90% in group C (odds ratio, 0.019; 95% confidence interval [CI], 0.01-0.31; p < .001). The frequency of catheter breakage due to catheter shear was significantly lower in group I (0%) than in group C (80%; p < .001). The mean tension and displacement required to break the catheter were significantly higher in group I than in group C (4.13 ± 0.37 N vs. 3.14 ± 1.00 N; mean difference, 0.99 N; 95% CI, 0.25-1.73 N; p = .013 and 222 ± 59.9 mm vs. 122 ± 77.7 mm; mean difference, 100 mm; 95% CI, 34.1-165 mm; p = .005). CONCLUSIONS: Our improved epidural tunneling technique, which was designed for pediatric cases, could reduce the risk of catheter shear.

HMGB1 Promotes Intraoral Palatal Wound Healing through RAGE-Dependent Mechanisms.

High mobility group box 1 (HMGB1) is tightly connected to the process of tissue organization upon tissue injury. Here we show that HMGB1 controls epithelium and connective tissue regeneration both in vivo and in vitro during palatal wound healing. Heterozygous HMGB1 (Hmgb1+/-) mice and Wild-type (WT) mice were subjected to palatal injury. Maxillary tissues were stained with Mallory Azan or immunostained with anti-HMGB1, anti-proliferating cell nuclear antigen (PCNA), anti-nuclear factor-κB (NF-κB) p50 and anti-vascular endothelial growth factor (VEGF) antibodies. Palatal gingival explants were cultured with recombinant HMGB1 (rHMGB1) co-treated with siRNA targeting receptor for advanced glycation end products (RAGEs) for cell migration and PCNA expression analysis. Measurement of the wound area showed differences between Hmgb1+/- and WT mice on Day 3 after wounding. Mallory Azan staining showed densely packed of collagen fibers in WT mice, whereas in Hmgb1+/- mice weave-like pattern of low density collagen bundles were present. At three and seven days post-surgery, PCNA, NF-κB p50 and VEGF positive keratinocytes of WT mice were greater than that of Hmgb1+/- mice. Knockdown of RAGE prevents the effect of rHMGB1-induced cell migration and PCNA expression in gingival cell cultures. The data suggest that HMGB1/RAGE axis has crucial roles in palatal wound healing.

[Anesthetic Management for Pacemaker Implantation in a Child with Mitochondrial Diseases and Complete Atrioventricular Block].

A 12-year-old boy with mitochondrial encephalomy- opathy underwent pacemaker implantation for com- plete atrioventricular block. He was hospitalized as his general condition deteriorated. Furthermore, Holter electrocardiogram revealed rapid atrioventricular con- duction defect Anesthesia was induced with propofol, fentanyl, and rocuronium and maintained with continuous infusion of propofol and remifentanil with administration of fen- tanyl and rocuronium under neuromuscular monitoring during surgery. Bispectral index was monitored and maintained at approximately 40. He could not commu- nicate and had unstable circulation. Therefore, we pro- longed the anesthesia induction time. In addition, for the purpose of decreasing the amount of anesthetic required, an ultrasound-guided transversus abdominis plane block was performed. Throughout the periopera- tive period, neither cardiovascular instabilities nor pro- gression of metabolic acidosis and sudden body tem- perature increases were observed. Many important points must be considered when administering anesthesia to a child with mitochondrial disease. When we plan the anesthetic strategy, moni- toring, and so on properly, the appropriate anesthesia management can be performed.

[Perioperative Management for Atlantoaxial Rotatory Fixation in a Child with Down Syndrome].

Atlantoaxial instability is a relatively common com- plication in children with Down syndrome. Atlantoaxial rotatory fixation (AARF) is a condition in which the atlantoaxial joint is fixed at the position of rotation deformity accompanied by pain. We report a 10-year-old girl with Down syndrome who developed AARF postoperatively. No symptoms had been present prior to surgery. During anesthesia induction and then surgery, her neck was maintained at rest However, there was intense body movement during extubation. On postoperative day 8, she experi- enced sudden onset of neck pain and neck exercise restrictions, and a neck sprain was thus diagnosed. The symptoms gradually improved with analgesic administration and rehabilitation, but complete recovery was not obtained. Therefore, on postoperative day 23, cervical radiography and computed tomography were performed. These imaging studies revealed AARF. She was given conservative treatment We conclude that preoperative evaluation and peri- operative protection of the cervical spine are important Considering the mental retardation characteristic of Down syndrome, it is essential to diagnose and treat AARF at the earliest possible stage based on careful observation.

[Anesthetic management of a patient with metatropic dysplasia].

A 5-year-old girl with metatropic dysplasia was scheduled for an operation of posterior cervical fusion. This disease is a rare skeletal dysplasia characterized by long trunk and short limbs and severe scoliosis. As she had been suspected to have a difficult airway, we attempted fiberoptic intubation with a nasopharyngeal airway to prevent airway obstruction. The nasopharyngeal airway ensured a patent airway sufficient oxygenation, and anesthesia. Thus, it was possible to perform a fiberoptic intubation via the opposite nostril with no adverse event. The combination of a nasopharyngeal airway and fiberoptic guided tracheal intubation is a reliable and safe procedure for small children with metatropic dysplasia and difficult airway.

[Anesthetic management for a case of an isolated congenital unilateral absence of the right pulmonary artery].

Isolated unilateral absence of the right pulmonary artery without any intracardiac anomaly (APA) is a rare congenital cardiovascular disorder. We report a case of a 47-day-old female infant with right APA who underwent pulmonary angiogram under general anesthesia. Induction and maintenance of anesthesia consisted of total intravenous anesthesia with propofol, remifentanil and vecuronium. Hemodynamic status and oxygenation were stable throughout the examination. Mean pulmonary artery pressure was 22 mmHg. During bronchofiberscopic examination through an endotracheal tube, SpO2 rapidly decreased from 98% to 50% in 10 s despite sufficient preoxygenation with 100% oxygen. Our case suggests that a care must be taken for desaturation during procedures without ventilation in PAP patients.

Obstructive shock due to tracheal perforation following long-term placement of a tracheostomy tube in a pediatric patient: a case report.

BACKGROUND: Tracheal perforation, although rare, is a known late complication of tracheostomy tube placement. CASE PRESENTATION: We present a 7-year-old boy with severe physical and mental disabilities under tracheostomy and long-term mechanical ventilation and steroid therapy who suddenly developed obstructive shock secondary to pneumomediastinum and pneumothorax. Prior bronchoscopy had shown the tip of the tracheostomy tube contacting the posterior tracheal wall, causing ulceration and subsequent tracheal perforation. The perforation was bridged using a cuffed tracheostomy tube, but the patient subsequently died of additional comorbidities. CONCLUSIONS: Our experience suggests that tracheal perforation should be considered when pediatric patients with tracheostomy tubes suddenly develop hypotension.

Tracheal extubation of anesthetized pediatric patients with heart disease decreases the incidence of emergence agitation: A retrospective study.

Background: Emergence agitation for pediatric patients after general anesthesia is one of the postoperative complications. The relationship between consciousness at tracheal extubation and emergence agitation is not clear. Aim: The aim of the present study was to determine whether tracheal extubation of anesthetized pediatric patients with heart disease by propofol decreases the incidence of emergence agitation. Settings and Design: This was a retrospective case-control study conducted at a children's hospital. Materials and Methods: Pediatric patients with heart disease aged 0-14 years who underwent cardiac catheterization under general anesthesia by propofol between October 2014 and September 2018 were enrolled. The incidence of emergence agitation by anesthetized extubation was compared with that by awake extubation. Statistical Analysis Used: Logistic regression analysis was performed. Results: Anesthetized extubation was performed in 202 patients and awake extubation was performed in 56 patients. The incidence of emergence agitation was significantly lower in patients who underwent anesthetized extubation than in patients who underwent awake extubation (25.2% vs. 69.6%, P = 0.000). In logistic regression analysis, anesthetized extubation [odds ratio (OR): 0.075, 95% confidence interval (CI): 0.034-0.165, P = 0.000] and older age (OR: 0.808, 95% CI: 0.728-0.897, P = 0.000) were associated with a decreased incidence of emergence agitation, and preoperative anxiety (OR: 2.220, 95% CI: 1.060-4.660, P = 0.03) was associated with an increased incidence of emergence agitation. Conclusions: Tracheal extubation under anesthesia by propofol decreases the incidence of emergence agitation in pediatric patients with heart disease.

1,5-Anhydro-D-fructose attenuates lipopolysaccharide-induced cytokine release via suppression of NF-kappaB p65 phosphorylation.

Lipopolysaccharide (LPS) stimulates macrophages by activating NF-kappaB, which contributes to the release of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6. 1,5-Anhydro-D-fructose (1,5-AF), a monosaccharide formed from starch and glycogen, exhibits anti-oxidant activity and enhances insulin secretion. This study examined the effects of 1,5-AF on LPS-induced inflammatory reactions and elucidated its molecular mechanisms. Before LPS challenge, mice were pretreated with 1,5-AF (38.5 mg/kg). We found that 1,5-AF pretreatment attenuated cytokine release into the serum, including TNF-alpha, IL-6 and macrophage chemoattractant protein (MCP)-1. Furthermore, pretreatment with 1,5-AF (500 microg/ml) attenuated cytokine release, and 1,5-AF directly inhibited the nuclear translocalization of the NF-kappaB p65 subunit in LPS-stimulated murine macrophage-like RAW264.7 cells. This inhibition was responsible for decreased LPS-induced phosphorylation on Ser536 of the NF-kappaB p65 subunit, which is a posttranslational modification involved in the non-canonical pathway. Collectively, these findings indicate that the anti-inflammatory activity of 1,5-AF occurs via inactivation of NF-kappaB.

Attenuation of LPS-induced iNOS expression by 1,5-anhydro-d-fructose.

1,5-anhydro-d-fructose (1,5-AF), a monosaccharide formed from starch and glycogen, exhibits antioxidant and antibacterial activity, and inhibits cytokine release by attenuating NF-kappaB activation in LPS-stimulated mice. The present study examined whether 1,5-AF inhibits lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) in vitro and in vivo. We found that 1,5-AF significantly blocked the production of NO, and protein and mRNA expression of iNOS, and up-regulated IL-10 production in vitro. We also investigated the effects of 1,5-AF on acute lung inflammation in C57BL/6J mice. We found that protein and mRNA expression of iNOS in lung tissues were inhibited by 1,5-AF pretreatment. In addition, the serum level of IL-10 was upregulated by 1,5-AF. Collectively, the iNOS transcriptional and translational inhibitory effects of 1,5-AF seem to be prolonged and enhanced by the production of IL-10. These results suggest that 1,5-AF could be a useful adjunct in the treatment of acute lung inflammation.

Minocycline attenuates both OGD-induced HMGB1 release and HMGB1-induced cell death in ischemic neuronal injury in PC12 cells.

High mobility group box-1 (HMGB1), a non-histone DNA-binding protein, is massively released into the extracellular space from neuronal cells after ischemic insult and exacerbates brain tissue damage in rats. Minocycline is a semisynthetic second-generation tetracycline antibiotic which has recently been shown to be a promising neuroprotective agent. In this study, we found that minocycline inhibited HMGB1 release in oxygen-glucose deprivation (OGD)-treated PC12 cells and triggered the activation of p38mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinases (ERK1/2). The ERK kinase (MEK)1/2 inhibitor U-0126 and p38MAPK inhibitor SB203580 blocked HMGB1 release in response to OGD. Furthermore, HMGB1 triggered cell death in a dose-dependent fashion. Minocycline significantly rescued HMGB1-induced cell death in a dose-dependent manner. In light of recent observations as well as the good safety profile of minocycline in humans, we propose that minocycline might play a potent neuroprotective role through the inhibition of HMGB1-induced neuronal cell death in cerebral infarction.

Edaravone attenuates cerebral ischemic injury by suppressing aquaporin-4.

Aquaporin-4 (AQP4) plays a role in the generation of post-ischemic edema. Pharmacological modulation of AQP4 function may thus provide a novel therapeutic strategy for the treatment of stroke, tumor-associated edema, epilepsy, traumatic brain injury, and other disorders of the central nervous system (CNS) associated with altered brain water balance. Edaravone, a free radical scavenger, is used for the treatment of acute ischemic stroke (AIS) in Japan. In this study, edaravone significantly reduced the infarct area and improved the neurological deficit scores at 24h after reperfusion in a rat transient focal ischemia model. Furthermore, edaravone markedly reduced AQP4 immunoreactivity and protein levels in the cerebral infarct area. In light of observations that edaravone specifically inhibited AQP4 in a rat transient focal ischemia model, we propose that edaravone might reduce cerebral edema through the inhibition of AQP4 expression following cerebral infarction.

The free radical scavenger edaravone rescues rats from cerebral infarction by attenuating the release of high-mobility group box-1 in neuronal cells.

Edaravone, a potent free radical scavenger, is clinically used for the treatment of cerebral infarction in Japan. Here, we examined the effects of edaravone on the dynamics of high-mobility group box-1 (HMGB1), which is a key mediator of ischemic-induced brain damage, during a 48-h postischemia/reperfusion period in rats and in oxygen-glucose-deprived (OGD) PC12 cells. HMGB1 immunoreactivity was observed in both the cytoplasm and the periphery of cells in the cerebral infarction area 2 h after reperfusion. Intravenous administration of 3 and 6 mg/kg edaravone significantly inhibited nuclear translocation and HMGB1 release in the penumbra area and caused a 26.5 +/- 10.4 and 43.8 +/- 0.5% reduction, respectively, of the total infarct area at 24 h after reperfusion. Moreover, edaravone also decreased plasma HMGB1 levels. In vitro, edaravone dose-dependently (1-10 microM) suppressed OGD- and H(2)O(2)-induced HMGB1 release in PC12 cells. Furthermore, edaravone (3-30 microM) blocked HMGB1-triggered apoptosis in PC12 cells. Our findings suggest a novel neuroprotective mechanism for edaravone that abrogates the release of HMGB1.

Proteolytic cleavage of high mobility group box 1 protein by thrombin-thrombomodulin complexes.

OBJECTIVE: High mobility group box 1 protein (HMGB1) was identified as a mediator of endotoxin lethality. We previously reported that thrombomodulin (TM), an endothelial thrombin-binding protein, bound to HMGB1, thereby protecting mice from lethal endotoxemia. However, the fate of HMGB1 bound to TM remains to be elucidated. METHODS AND RESULTS: TM enhanced thrombin-mediated cleavage of HMGB1. N-terminal amino acid sequence analysis of the HMGB1 degradation product demonstrated that thrombin cleaved HMGB1 at the Arg10-Gly11 bond. Concomitant with the cleavage of the N-terminal domain of HMGB1, proinflammatory activity of HMGB1 was significantly decreased (P<0.01). HMGB1 degradation products were detected in the serum of endotoxemic mice and in the plasma of septic patients with disseminated intravascular coagulation (DIC), indicating that HMGB1 could be degraded under conditions in which proteases were activated in the systemic circulation. CONCLUSIONS: TM not only binds to HMGB1 but also aids the proteolytic cleavage of HMGB1 by thrombin. These findings highlight the novel antiinflammatory role of TM, in which thrombin-TM complexes degrade HMGB1 to a less proinflammatory form.

Mechanism of HMGB1 release inhibition from RAW264.7 cells by oleanolic acid in Prunus mume Sieb. et Zucc.

High mobility group box-1 protein (HMGB1), primarily from the nucleus, is released into the extracellular milieu either passively from necrotic cells or actively through secretion by monocytes/macrophages. Extracellular HMGB1 acts as a potent inflammatory agent by promoting the release of cytokines such as tumor necrosis factor (TNF)-alpha, has procoagulant activity, and is involved in death due to sepsis. Accordingly, HMGB1 is an appropriate therapeutic target. In this study, we found that an extract of Prunus mume Sieb. et Zucc. (Ume) fruit (Ume extract), an abundant source of triterpenoids, strongly inhibited HMGB1 release from lipopolysaccharide (LPS)-stimulated macrophage-like RAW264.7 cells. The inhibitory effect on HMGB1 release was enhanced by authentic oleanolic acid (OA), a naturally occurring triterpenoid. Similarly, the HMGB1 release inhibitor in Ume extract was found to be OA. Regarding the mechanisms of the inhibition of HMGB1 release, the OA or Ume extract was found to activate the transcription factor Nrf2, which binds to the antioxidative responsive element, and subsequently the heme oxygenase (HO)-1 protein was induced, indicating that the inhibition of HMGB1 release from LPS-stimulated RAW264.7 cells was mediated via the Nrf2/HO-1 system; an essentially antioxidant effect. These results suggested that natural sources of triterpenoids warrant further evaluation as 'rescue' therapeutics for sepsis and other potentially fatal systemic inflammatory disorders.