[Anchor Fast endotracheal tube securing device for a pediatric patient during therapeutic hypothermia].

A 5-year-old girl was admitted to our hospital after resuscitation from cardiac arrest due to near-drowning accident in a river. On admission, Glasgow Coma Scale score was 7; arterial blood pressure was 113/73 mm Hg; heart rate was 157 beats x min(-1), and percutaneous oxygen saturation was 99% on 10 l x min(-1) of oxygen. The patient was intubated with a 5.0 mm internal diameter endotracheal tube, and therapeutic hypothermia was started for neural protection. Hypothermia in the target temperature of 34 degrees C was maintained for 24 hours using Arctic Sun System. Although the patient had been sedated with fentanyl 0.6-1.2 microg x kg(-1) x hr(-1), midazolam 0.2-0.4 mg x kg(-1) x hr(-1) and dexmedetomidine 0.6-1.0 mirog x kg(-1) x hr(-1), agitation increased during the rewarming period following hypothermia. To avoid accidental extubation, we used Anchor Fast as a device for securing oral endotracheal tube. Anchor Fast kept the tube position properly even though the patient was turned or moved. Seventy-two hours later, she was rewarmed and extubated as scheduled. Ten days after admission, she was discharged without any neurological deficits.

[Nasal high-flow therapy in a patient with postanesthetic hypoxia after tracheal extubation].

A 63-year-old female with obesity (body mass index of 32.0 kg x m(-2)) was scheduled for total abdominal hysterectomy under combined epidural general anesthesia. The surgical procedure was completed without any troubles. Immediately after tracheal extubation, however, the patient developed acute respiratory distress, and the percutaneous oxygen saturation (Spo2) decreased from 97 to 44% for 1 minute. When the patient was admitted to our intensive care unit due to hypoxia, arterial blood gas values showed pH 7.37, Paco2 40.4 mmHg, Pao2 67.5 mmHg, and Spo2 94% on 5 l x min(-1) of oxygen via face mask. Her respiratory rate was 23 breaths x min(-1). We used a nasal high-flow humidified oxygen system (Optiflow) to improve oxygenation. We set the initial flow rate at 35 l x min(-1) with 50% oxygen. One hour after initiating the nasal high-flow system, the patient's respiratory rate fell to 18 breaths x min(-1), and Spo2 rose up to 98%. Arterial blood gas showed improved Pao2 of 98.0 mmHg. Nasal high-flow therapy was useful to avoid intubation in a patient with postanesthetic respiratory failure.

Clinical dose of lidocaine destroys the cell membrane and induces both necrosis and apoptosis in an identified Lymnaea neuron.

PURPOSE: Although lidocaine-induced cell toxicity has been reported, its mechanism is unclear. Cell size, morphological change, and membrane resistance are related to homeostasis and damage to the cell membrane; however, the effects of lidocaine on these factors are unclear. Using an identified LPeD1 neuron from Lymnaea stagnalis, we sought to determine how lidocaine affects these factors and how lidocaine is related to damage of the cell membrane. METHODS: Cell size and morphological form were measured by a micrograph and imaging analysis system. Membrane potential and survival rate were obtained by intracellular recording. Membrane resistance and capacitance were measured by whole-cell patch clamp. Phosphatidyl serine and nucleic acid were double stained and simultaneously measured by annexin V and propidium iodide. RESULTS: Lidocaine at a clinical dose (5-20 mM) induced morphological change (bulla and bleb) in the neuron and increased cell size in a concentration-dependent manner. Membrane potential was depolarized in a concentration-dependent manner. At perfusion of more than 5 mM lidocaine, the depolarized membrane potential was irreversible. Lidocaine decreased membrane resistance and increased membrane capacitance in a concentration-dependent manner. Both phosphatidyl serine and nucleic acid were stained under lidocaine exposure in a concentration-dependent manner. CONCLUSIONS: A clinical dose of lidocaine greater than 5 mM destroys the cell membrane and induces both necrosis and apoptosis in an identified Lymnaea neuron.

Lidocaine treatment during synapse reformation periods permanently inhibits NGF-induced excitation in an identified reconstructed synapse of Lymnaea stagnalis.

PURPOSE: Nerve growth factor (NGF) has been reported to affect synaptic transmission and cause neuropathic pain. In contrast, lidocaine has been used to reduce neuropathic pain; however, the effect of NGF and lidocaine on spontaneous transmitter release and synapse excitation has not been fully defined. Therefore, the effect of NGF and lidocaine on nerve regeneration, synapse reformation, and subsequent spontaneous transmitter release was investigated. We used Lymnaea stagnalis soma-soma-identified synaptic reconstruction to demonstrate that a transient increase in both frequency and amplitude of spontaneous events of miniature endplate potentials (MEPPs) occurs following NGF treatment and a short burst of action potentials in the presynaptic cell; in addition, the effect of lidocaine on NGF-induced synapse reformation was investigated. METHODS: Using a cell culture and electrophysiological and FM-143 imaging techniques for exocytosis on unequivocally identified presynaptic visceral dorsal 4 (VD4) and postsynaptic somata left pedal (LPeE) neurons from the mollusc Lymnaea stagnalis, the effects of NGF and lidocaine on nerve regeneration, synapse reformation, and its electrophysiological spontaneous synaptic transmission between cultured neurons were described. RESULTS: NGF increased axonal growth, frequency, and amplitudes of MEPPs. Lidocaine exposure during synapse reformation periods was drastically and permanently reduced axonal growth and the incidence of synapse excitation by NGF. CONCLUSION: NGF increased amplitudes and frequencies of MEPPs and induced synaptic excitation by increasing axonal growth and exocytosis. Lidocaine exposure during synapse reformation periods permanently suppressed NGF-induced excitation by suppressing axonal growth and exocytosis of presynaptic neurons in the identified reconstructed synapse of L. stagnalis.

Capsaicin indirectly suppresses voltage-gated Na+ currents through TRPV1 in rat dorsal root ganglion neurons.

BACKGROUND: Capsaicin is used to treat a variety of types of chronic pain, including arthritis and trigeminal neuralgia. Although the cellular effects of capsaicin have been widely studied, little is known about the effects of capsaicin on intracellular sodium ([Na(+)]i) concentrations and voltage-gated Na(+) currents (INa(+)) in nociceptive afferent neurons. Therefore, in this study we sought to characterize the effect of capsaicin on tetrodotoxin-sensitive (TTX-s) and resistant (TTX-r) INa(+). METHODS: The effects of capsaicin on INa(+) in rat dorsal root ganglion neurons were studied for both TTX-s and TTX-r components using whole-cell patch-clamp techniques and intracellular sodium imaging. RESULTS: In both TTX-s and TTX-r INa(+) of capsaicin-sensitive neurons, capsaicin (0.1 to 10 µM) reduced inward currents in a dose-dependent manner. Capsaicin induced a hyperpolarization shift in the steady-state inactivation curves. SB366791 (10 µM), a potent and selective transient receptor potential vanilloid member1 (TRPV1) antagonist, significantly attenuated the reduction in INa(+). Capsaicin induced an increase in the [Na(+)]i, and SB366791 (10 µM) significantly reduced the [Na(+)]i increase. An increase in [Na(+)]i with gramicidin also dependently suppressed INa(+) and induced a hyperpolarization shift in the steady-state inactivation curves by increasing the [Na(+)]i. CONCLUSION: The findings suggest that capsaicin decreases both TTX-s and TTX-r INa(+) as a result of an increase in [Na(+)]i through TRPV1.

Effects of orexin-A on propofol anesthesia in rats.

PURPOSE: An active sleep homeostatic process is present during propofol anesthesia. Activation of the orexin system induces wakefulness, and inhibition of the orexin system causes narcolepsy. We hypothesized that orexin would affect propofol anesthesia. METHODS: The effects of an intracerebroventricular (i.c.v.) injection of orexin-A (OXA) or an orexin-1 (OX-1) receptor antagonist, SB-334867, on the times to the loss and return of the righting reflex induced by propofol were examined in Wistar rats. The effects of propofol or OXA on norepinephrine (NE) and dopamine (DA) release from the prefrontal cortex (PFC) were examined using in vivo microdialysis. RESULTS: An i.c.v. injection of OXA (1 nmol) decreased the time to emergence from propofol anesthesia mediated by the OX-1 receptor without changing anesthetic induction (n = 8). An i.c.v. injection of SB-334867 (5 and 50 nmol) increased the time to emergence from propofol anesthesia without changing anesthetic induction (n = 8). Intravenous infusion of propofol decreased NE (48 ± 8%; n = 8) and DA (61.2 ± 11%; n = 8) release from PFC mediated by the GABA(A) receptor. An i.c.v. injection of OXA reversed the decreases in NE and DA release induced by propofol mediated by the OX-1 receptor (n = 8). CONCLUSION: These results indicate that the orexin system may accelerate the emergence from propofol anesthesia associated with increases in the central noradrenergic and dopaminergic activity.

Lidocaine depolarizes the mitochondrial membrane potential by intracellular alkalization in rat dorsal root ganglion neurons.

PURPOSE: The mitochondrial membrane potential (ΔΨm) is an important factor for apoptosis, and it is produced by the proton electrochemical gradient (ΔµH(+)). Therefore, the intracellular proton concentration (pH(in)) is an important factor for modifying the ΔΨm. However, the effects of lidocaine on pH(in) are unclear. To investigate mitochondrial responses to lidocaine, therefore, we simultaneously measured pH(in) with ΔΨm, flavin adenine dinucleotide (FAD), and reduced form of nicotinamide adenine dinucleotide (NADH) fluorescence, and calculated the FAD/NADH ratio (redox ratio), the superoxide production in mitochondria. METHODS: Morphological change and early apoptosis were observed by annexin-V FITC staining under fluorescent microscope. The ratiometric fluorescent probe JC-1 and HPTS were used for the simultaneous measurements of ΔΨm with pH(in) in rat dorsal root ganglion (DRG) neurons. FAD and NADH autofluorescence were simultaneously measured, and the FAD/NADH fluorescence ratio (redox ratio) was calculated. The superoxide was measured by mitosox-red fluorescent probe for mitochondrial superoxide. Lidocaine was evaluated at 1, 5, and 10 mM. RESULTS: Morphological change and early apoptosis were observed after 10 mM lidocaine administration. Lidocaine depolarized ΔΨm with increased pH(in) in a dose-dependent manner. In low-pH saline (pH 6), in the presence of both the weak acids (acetate and propionate), lidocaine failed to depolarize ΔΨm and increase pH(in). On the other hand, lidocaine decreased the redox ratio in the cell and increased the levels of superoxide in a dose-dependent manner. CONCLUSION: These results demonstrated that lidocaine depolarizes ΔΨm by intracellular alkalization. These results may indicate one of the mechanisms responsible for lidocaine-induced neurotoxicity.

The usefulness of plasma levels of mature and total adrenomedullin as biomarkers indicating the magnitude of surgical stress responses: A single-center, prospective, observational study.

BACKGROUND AND AIM: Adrenomedullin (AM), a vasodilatory peptide, is known for its pleiotropic actions. AM levels are increased under inflammatory conditions such as sepsis and can be useful as a prognostic biomarker. However, there are only a few reports on the physiological actions of AM in the perioperative period. The aim of this single-center, prospective, and observational study was to investigate the changes in the plasma levels of mature AM (mAM) and total AM (tAM) observed during the perioperative period. In addition, we aimed to determine the association between each AM level and immune-inflammatory parameters to explore the usefulness of AM as a biomarker of the magnitude of surgical stress responses. METHODS: The levels of both mAM and tAM, in addition to the levels of presepsin, interleukin-6, procalcitonin, white blood cell, and C-reactive protein, were measured in blood samples obtained during the perioperative period. Other laboratory data, including sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation (APACHE) II scores, were obtained from individual clinical records. Correlations between each AM and clinical parameters were determined using Spearman's rank correlation. P<0.05 were considered statistically significant. RESULTS: One hundred and twenty-three perioperative patients scheduled for three types of surgical procedures, including cardiopulmonary bypass surgery, abdominal surgery, and cervical laminoplasty, were included in this study. There was a moderate to strong correlation between each AM and immune-inflammatory parameters, SOFA score, and APACHE II score, as related to surgical trauma. Specifically, the strongest correlation was observed between each AM and SOFA score. CONCLUSIONS: These findings suggest that plasma AM levels may represent the most important inflammatory mediators that are evident in surgical stress responses. RELEVANCE FOR PATIENTS: Since the levels of both tAM and mAM show the same trend, mAM and tAM may be equally used as biomarkers for the evaluation of the physiological status of surgical patients. TRIAL REGISTRATION: This observational study was retrospectively registered with Japanese Clinical Trial Registry "UMIN-CTR" on March 19, 2018, and was given a trial ID number UMIN000031792.

The diagnostic and prognostic value of mature and total adrenomedullin for sepsis: a prospective observational study.

INTRODUCTION: Information about biologically active adrenomedullin (mature AM), a potential new biomarker for sepsis and septic shock, is limited. Here, we investigated the value of mature AM for diagnosis and outcome prediction in sepsis. MATERIAL AND METHODS: Patients admitted to the intensive care unit (ICU) were retrospectively cate-gorised into non-sepsis or sepsis groups, according to the Sepsis-3 definitions. Plasma levels of mature and total (the sum of the levels of intermediate and mature forms) AM were measured, and their usefulness was compared with that of other sepsis biomarkers, such as procalcitonin and presepsin. RESULTS: Of the 98 patients analysed, 42 were assigned to the non-sepsis and 56 to the sepsis group. Mature and total AM levels on admission were significantly higher in patients with than in those without sepsis. The areas under the receiver operating characteristic curves (AUCs) of mature and total AM for diagnosing sepsis were 0.85 and 0.88, whereas those of procalcitonin and presepsin were 0.83 and 0.68, respectively. AUCs of mature and total AM for predicting 28-day mortality in patients with sepsis became significant on day 3 after admission. A good correlation between the AM forms was found, indicating that changes in their plasma levels may directly reflect each other. CONCLUSIONS: Because mature and total AM levels increased significantly in patients with sepsis on admission, both forms may be used as reliable and early biomarkers for diagnosing sepsis according to the Sepsis-3 definitions. However, prediction of 28-day mortality in such patients would require several days of ICU stay.

A case of severe acute exacerbation of Yokkaichi asthma treated with a vibrating mesh nebulizer.

Yokkaichi asthma was one of the most common environmental pollution diseases in Japan in the 1960s and 1970s. The problem of air pollution in Yokkaichi was solved in the 1970s. However, mortality and life expectancy were still affected by the late effects of air pollution in patients with Yokkaichi asthma even in the 2000s. In this case report, we described the experience of successful treatment of a patient with severe asthmatic status due to Yokkaichi asthma. A 40s-year-old man, who was officially certified as a patient with Yokkaichi asthma from his infancy, was admitted to hospital due to acute exacerbation of asthma. Mechanical ventilation, intravenous administration of aminophylline and dexamethasone, enteral administration of montelukast, and a transdermal patch of tulobuterol were started. However, because of the lack of improvement in clinical status, inhalation of procaterol using vibrating mesh nebulizer systems was started. Inhalation of procaterol was used three times a day. After using the vibrating mesh nebulizer, respiratory system compliance and hypercapnia rapidly improved. Bilateral expiratory wheezing was diminished. Weaning from mechanical ventilation was initiated, and on the eighth day of mechanical ventilation, the patient was extubated. Although intractable respiratory failure with decreased respiratory system compliance resulting from the late effects of air pollution and a long-time asthmatic inflammatory condition was observed, the use of a vibrating mesh nebulizer for the inhaled administration of procaterol was useful to relieve severe bronchospasm due to Yokkaichi asthma.

[Optimal dose of fentanyl for postoperative epidural analgesia after cesarean section].

BACKGROUND: The aim of this study was to investigate which dose of fentanyl in ropivacaine for epidural anesthesia will provide effective analgesia with minimal side effects after cesarean section (CS). METHODS: Fifty eight patients scheduled for CS were randomly allocated to two groups according to fentanyl dose in epidural analgesia: group F1 (11 microg x hr(-1); n=30) or group F 2 (21 microg x hr(-1); n= 28). Ropivacaine 0.2% 100 ml with fentanyl 400 or 800 microg was administered into the epidural space in the groups F1 and F 2, respectively. Pain scores (visual analogue scale: VAS) with cough or movement, Bromage score, incidence of diclofenac or pentazocine administration, satisfaction score (VAS) and side effects (nausea, vomiting and pruritus) were recorded after CS. RESULTS: Pain scores with cough or movement were significantly lower in the group F 2 than the group F 1 at twelve and twenty-four hours after CS. Bromage score at twelve hours was lower in the group F 2 than the group F 1. The incidences of side effects were similar between the two groups. Satisfaction score was significantly higher in the group F 2 than the group F 1. CONCLUSIONS: We conclude that continuous epidural administration of fentanyl 21 microg x hr(-1) with ropivacaine provides the optimum balance between pain relief and side effects compared with fentanyl 11 microg x hr(-1) with ropivacaine after CS.

New insights concerning insulin synthesis and its secretion in rat hippocampus and cerebral cortex: amyloid-ß1-42-induced reduction of proinsulin level via glycogen synthase kinase-3ß.

The reduction of insulin levels in hippocampal areas is associated with Alzheimer's disease. The present study using rat brain explores the mechanisms of insulin synthesis and secretion, as well as amyloid-ß1-42 (Aß(1-42))-induced reduction of proinsulin expression. After confirming the expression of insulin mRNA and proinsulin in rat brain, we visualized and analyzed the motion of insulin secretion in rat hippocampal neurons using pH-sensitive green fluorescent protein (pHluorin) fused to the insulin. In the rat hippocampal neurons expressing insulin-pHluorin, time-lapse confocal laser scanning microscopy revealed the appearance of fluorescent spots induced by depolarization after stimulation with 50 mM KCl. In these fluorescent spots, Ca(2+)-dependent activator protein for secretion 2 (CAPS2), which is the regulator of the dense-core vesicle involving neuronal peptides, was co-localized with insulin-pHluorin. However, Aß(1-42)-induced reduction of proinsulin in rat hippocampal neurons was inhibited by treatment with lithium and transfection with glycogen synthase kinase-3ß (GSK-3ß) siRNA. These results demonstrate that synthesized insulin is secreted from rat hippocampal and cortical neuron's dense-core vesicles, and that activation of GSK-3ß in Aß(1-42)-induced Alzheimer's model hippocampal neurons decreases the insulin synthesis.