Okinawa has long been a world-famous area of longevity. Recently, however, an expansion of lifestyle-related metabolic and cardiovascular diseases (e.g. metabolic syndrome, diabetes mellitus, dyslipidemia and hypertension) in Okinawa has been linked with a substantial drop in life span (Okinawa Crisis). Despite a mild increase in exaggerated body fat mass, the risk for diabetes mellitus is known to elevate substantially. By nature, body weight homeostasis is critically regulated by the inter-tissue communications between brain and peripheral tissues. To survive starvation, the cold, and water/salt deficiencies, our physiologic systems have evolved in favor of fat storage and sodium retention, hence the global increase in obesity-diabetes-hypertension syndrome given today's caloric excess and sedentary lifestyle. Recent research has unveiled the molecular mechanisms of fuel homeostasis. For example, the adipocyte-derived hormone leptin strongly controls appetite and fuel homeostasis via the hypothalamus. However, clinical application of leptin for the treatment of obesity-diabetes syndrome has been hampered by the fact that leptin action is deteriorated on a high-fat, westernized diet. In this article, the update around the medicine of obesity and metabolic syndrome is reviewed with particular focus on the novel molecular and cellular mechanisms of preference for fatty foods.

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  Japanese physicians work long hours compared with developed countries such as the United States, Germany and France. Long work of physicians might induce not only health problems of physicians but also medical malpractice. However, more than half of Japanese hospitals with 200 beds or more founded by local governments perform illegal personnel management, such as working more hours than legal limit and working overtime without pay. In order to prevent physician burnout and medical malpractice, proper personnel management should be done in Japanese hospitals.

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  Malignant hyperthermia (MH) is an autosomal pharmacogenetic disease triggered by volatile halogenated anesthetics and/or depolarizing muscle relaxants. An MH reaction is life-threatening and is caused by an abnormally high release of myoplasmic Ca²⁺ from the sarcoplasmic reticulum through the ryanodine receptor 1 (RYR1). Mutations in the RYR1 gene are the major cause of MH and central core disease (CCD). More than 200 variants of RYR1 and 3 variants of α1-subunit of the voltage-dependent L-type Ca²⁺ channel (CACNA1S) linked to MH and CCD have been identified, but only 30 mutations are recognized as causative for MH and/or CCD. Myotubes cultured from MH patients showed increased sensitivity to RYR1 activators (caffeine, halothane and 4-chloro-m-cresol). Halothane leads to a significant contracture in MH susceptible (MHS) skeletal muscle bundles and increases the rate of calcium-induced calcium release (CICR) in MHS skinned fibers. More recently, store-operated Ca²⁺ entry was reported to be activated by halothane in human MHS skeletal skinned fibers. Dantrolene, the only specific treatment for MH, reduces the elevated myoplasmic Ca²⁺ level generated with MH reaction, but the exact mechanism underlying its inhibitory effect is unknown. For purging volatile anesthetics, modern anesthesia workstations require more time to flush with a high-flow fresh gas (O₂).

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  Intraoperative awareness is hard on both patients and anesthesiologists. In this paper, several awareness cases are presented prior to the main discussion in the symposium of the monitoring for prevention of intraoperative awareness. Potential awareness cases which were noticed by electroencephalogram (EEG) monitoring are also presented.
  The main etiology of awareness is inadequate hypnotic and/or analgesic actions in a relative or absolute manner. Improper equipment or anesthesiologist human errors should be avoided. It is desirable to standardize anesthetic management to avoid primary mishaps.
  The processed EEG, such as BIS, is valuable in particular when the patient is paralyzed, since the electromyogram is reduced and they can't move to express awareness when muscle relaxants are used.
  When an anesthesiologist recognizes patient awareness, what is the best measure for the patient? Repeated explanations that awareness is inevitable and is under anesthesiologist control are desirable. The author believes that this might alleviate psychological harm to the patient.

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  Intraoperative awareness may lead to serious consequences postoperatively, lasting years in some patients. Prevention of unintended awareness is far more important than treatment. Mathematical processing of cortical electroencephalogram (EEG) as well as auditory evoked potential (EP) have been utilized as an objective, pharmacodynamic monitor of anesthetic effect on the brain. An ideal “depth of anesthesia” monitor should be able to clearly distinguish the awake state from the unconscious state and to function as a warning device of “impending awareness” in paralyzed patients. Unfortunately, no EEG monitors fulfill this requirement at present. Large-scale comparisons between BIS and end-tidal volatile agent monitoring have shown that both are equivalent in terms of the incidence of intraoperative awareness. Setting a lower alarm for expired inhalational anesthetics is therefore an easy, practical way to prevent awareness. Close observation of vascular access and infusion pumps is mandatory in total intravenous anesthesia. There have been some exceptional patients who were conscious despite showing BIS values within the manufacturer's recommended range. Titration of anesthetics, particularly reduction of drug concentration based solely on processed EEG index values, may inadvertently increase the risk of intraoperative awareness. Careful conduct of anesthesia, with end-tidal gas monitoring and using an EEG/EP monitor when feasible, is essential to avoid this potentially devastating complication.

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  The information derived from the isobologram, which shows the relationship between hypnotics and analgesics, including MAC reference lines, may be useful, because the current role of electroencephalogram-related monitors to prevent intra-operative awareness depends on the anesthetics used. The SmartPilot View, developed by Dräger Medical, simulates effect site concentrations of opioids, intravenous and volatile anesthetics. The status of anesthetic levels as a result of a combination of hypnosis and analgesia is expressed as a closed circle (isobole) on the isobologram. An isobole always shows both the current anesthetic status and the status 15 minutes in the future. The SmartPilot View is expected to contribute to the maintainance of adequate anesthesia levels as well as the prevention of intra-operative awareness, because anesthesiologists can obtain the current anesthesia status correctly and also intuitively.

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  It is well known that the central nervous system (CNS) is especially vulnerable to hypoxia and ischemia. Therefore, it is of great importance to deliver sufficient oxygen and glucose, which is the only source of energy metabolism in the CNS, by cerebral blood flow (CBF). As an introduction to the symposium on forefront neuroanesthesia, the following elementary items are described: CBF, cerebral metabolic rate of oxygen (CMRO₂), the effects of anesthetics on CBF and CMRO₂, intracranial pressure, CNS monitoring, i.e., transcranial Doppler ultrasonography, cerebral tissue oxygen saturation, evoked potential (auditory, visual, somatosensory, and motor), mechanisms of neuronal cell death by ischemia and reperfusion, and neuroprotective strategies focusing on xenon gas, hydrogen molecules, and protein transduction.

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  Carotid endarterectomy and carotid artery stenting have been widely accepted as the treatment options for preventing stroke in patients with carotid artery stenosis. These patients have several perioperative risks such as embolic or hemodynamic stroke, hyperperfusion syndrome, and adverse cardiac events. In order to decrease mortality and morbidity, it is necessary to provide a tailored approach on the basis of preoperative risk stratification, appropriate selection of treatment, and perioperative cerebral monitoring. In this article, we discuss the importance of the role of the anesthesiologist, who plays an active role in the perioperative care of such patients.

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  Neuroprotection and neuromonitoring is of clinical value in patients undergoing intracranial aneurysm surgery. Neuroprotective effects of mild hypothermia and barbiturate remain undetermined in such patients. Efficacy of beta-blocker, statin and magnesium has been also evaluated. As a supplement for clipping, adenosine has been used and its safety is currently under investigation. For neuromonitoring, motor evoked potentials have been extensively used during intracranial aneurysm surgery. For motor evoked potential monitoring, technique for motor cortex stimulation is most important. Combined use of recently developed high-luminosity stimulation device and electroretinography can provide reliable recording of visual evoked potential during neurosurgical procedures. Recent progress in neuroprotection and neuromonitoring in patients undergoing intracranial aneurysm surgery are described.

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  We, anesthesiologists should learn more the diagnostic and therapeutic backgrounds of brain tumors to perform better perioperative anesthetic management. Here, we introduce the backgrounds of meningioma and glioma that are the two most frequently encountered brain tumors in Japan. Then, we describe the fundamental anesthetic management for the brain tumor. Finally, we introduce modified monitoring of motor evoked potentials established by Hokkaido University.

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  Brain injury after cardiovascular surgery is associated with significantly reduced prognosis. The ability to predict and prevent brain injury during the perioperative period is thus important. There are two categories of brain damage after cardiac surgery: type 1, focal neurologic deficits, coma and stupor; and type 2, decline in intellectual function and memory impairment. These types have an incidence of 3.1% and 3.0%, respectively. With both types, mortality rates are increased. Important risk factors for brain injury after cardiovascular surgery include age, atherosclerosis of the central artery, intraaortic balloon pumping, diabetes mellitus, lung disease and alcohol abuse.
  Cardiopulmonary bypass (CPB) can induce brain injury after cardiovascular surgery, as CPB can evoke embolization, low perfusion rates and inflammatory response. As off-pump coronary artery bypass graft (OPCAB) significantly inhibits embolization and inflammatory response, we consider OPCAB to protect against brain injury after surgery. However, many reports suggest that these considerations are insufficient in low-risk patients.
  In aortic arch replacement, it is important to protect against cerebral ischemia during revascularization of the cervical artery. Methods of brain protection for aortic arch replacement include deep hypothermic circulatory arrest, selective antegrade cerebral perfusion and retrograde cerebral perfusion. These methods are selected according to patient risk and the policy of the specific institution. The optimal methods for brain protection remain unclear.

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  Levobupivacaine, the S (-) -enantiomer of bupivacaine, is a long-acting amino amide local anesthetic used worldwide. This drug was recently approved for peripheral nerve blocks in addition to epidural anesthesia in Japan. Peripheral nerve blocks are essential tools for analgesia following lower extremity surgery, providing higher patient satisfaction and selective analgesia with a lowered risk of complications. Levobupivacaine has excellent analgesic efficacy, similar to bupivacaine and superior to ropivacaine, and is associated with less CNS and cardiac toxicity than bupivacaine. Motor blockade from local anesthetics may be ideal in the OR, but prolonged motor weakness may involve delayed rehabilitation and increase the risk of falls. A continuous femoral nerve block with 0.1% levobupivacaine at 4 ml/h administration (96 mg/24 hr) provides suitable analgesia minimizing motor weakness in total knee arthroplasty. To prevent accidental falls, education for patients and correct catheter placement using ultrasound guidance are essential requirements, in addition to adjusting the dose of levobupivacaine.

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  Evaluation of systemic oxygen supply-demand balance is the first step of safe anesthetic management. Arterial oxygen saturation, hemoglobin concentration and cardiac output are particularly important factors in oxygen delivery. Mixed venous oxygen saturation reflects systemic oxygen supply-demand balance. The FloTrac/Vigileo system is an arterial blood pressure cardiac output monitor to estimate stroke volume from the standard deviation of arterial pressure. The PreSep central venous oximetry catheter is an oxygen supply-demand balance monitor to measure the central venous oxygen saturation instead of mixed venous oxygen saturation. In the management of critically ill patients, patient safety would be ensured and the burden of anesthesiologist could be reduced by taking advantage of these minimally invasive monitors.

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  Although epidural anesthesia has several advantages over general anesthesia, it has the disadvantage of prolonged postoperative recovery for motor function. We evaluated whether 20 mL of saline injected epidurally on removal of the catheter shortened the motor recovery from epidural ropivacaine anesthesia. Sixty patients who underwent transurethral surgery received lumbar epidural anesthesia with 10 mL of ropivacaine. At the end of surgery, the patients were randomly allocated to two groups, and 20 mL saline was injected epidurally in one group, whereas the other group was given none, upon removal of an epidural catheter. The motor block was assessed with the Bromage scale. The time to recovery of motor function in the saline group was significantly shorter (144 min) than in the control group (250 min). We believe that epidural injection of saline would be useful to shorten postoperative motor blockade.

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  We experienced a case in which pulse-less electrical activity occurred at the time of intrathecal drug injection. From a clinical standpoint, we considered that heart rate and blood pressure decreases were derived from the Bezold-Jarisch reflex, which was shown by heart rate variability analysis. Additionally, the pulse-less electrical activity might have been provoked because spinal anesthesia was performed without noticing the Bezold-Jarisch reflex. We concluded that it is important to check for the Bezold-Jarisch reflex emerging in patients in a sympathetically hypertonic state combined with a decrease in circulation volume.

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  A 71-year-old woman diagnosed with bilateral Zenker's diverticulum (ZD) was scheduled for diverticulectomy. ZD is a sac-like deformation in the posterior wall of the lower pharynx between the thyropharyngeal and cricopharyngeal muscles. Regurgitation at the induction of general anesthesia is one of the major concerns for anesthesiologists. According to previous reports, several treatments are recommended, such as aspiration of the diverticulum contents in pre-induction of anesthesia and rapid sequence induction in the heads-up position. Liquid meals for two days before the operation might be effective in this case. Also, anesthesiologists have to take extra precautions against hoarseness, and airway edema after extubation. It might be useful to observe diverticulum content directly by transnasal fiberoptic endoscopy before the induction of anesthesia. We were able to perform safe anesthetic management of the patient with ZD, which is a rare disease in Japan.

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  A five-year-old boy with hoarseness and stridor was scheduled for operation to treat laryngeal papillomatosis. A laryngoscopy five days before the operation revealed that the glottis was covered with papilloma, and the windpipe to the left of the glottis was barely visible. A rapid induction was scheduled, and the patient was placed in the right lateral position to facilitate tracheal intubation. It was found that the papilloma actually covered the whole of the glottis, and the trachea was not visible at all. Intubation was performed with a fiberscope. It was not possible to predict the rapid growth of the papilloma for a few days, however, adequate preoperative airway assessment and preparations for contingency enabled successful airway management. As pediatric laryngeal papillomatosis is highly recurrent and disseminated, the anesthesiologist must be particularly careful about airway management is needed in each case. For the accidental airway obstruction, anesthesiologists should cooperate with otorhinolaryngologists.

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  Trigemino-Cardiac-Reflex (TCR), which is not well known, occurs during stimulation of the sensory nerve of the trigeminal nerve mostly in head and neck surgery. This is a case report in which cardiac arrest occurred during endoscopic transsphenoidal pituitary surgery due to TCR, and we investigated the risk of TCR during surgery in the literature.

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  We evaluated rocuronium-induced neuromuscular blockade and its reversal with sugammadex in 2 pediatric patients with mild and severe Duchenne muscular dystrophy (DMD). After induction of anesthesia with propofol and fentanyl, patients initially received 0.6 mg/kg rocuronium and neuromuscular block was evaluated by contractions of the adductor pollicis muscle to ulnar nerve train-of-four (TOF) stimulation using an acceleromyograph. The onset times of rocuronium were 98 s and 2,102 s in mild and severe DMD patients. Subsequently, intense rocuronium-induced block was determined every 6 min using the post-tetanic count (PTC). Whenever the first response to the PTC stimulus was detected, 0.1 mg/kg rocuronium was additionally administered. When the PTC reappeared after the last dose of rocuronium, 4 mg/kg sugammadex was administered and the time to recover to a TOF ratio of 0.9 was 156 s and 423 s in mild and severe DMD patients, respectively.
  Our results indicate that onset and duration of action of rocuronium and sugammadex-facilitated recovery from neuromuscular blockade may be prolonged according to the severity of DMD.

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  A 73-year-old man was scheduled for nephrectomy for left renal cell carcinoma with tumor thrombus in the inferior vena cava (IVC). During the surgery, a sudden decrease in SpO₂, EtCO₂ and BP occurred, and tumor thrombus in the IVC disappeared on the TEE image. Pulmonary embolism was suspected. As hemodynamic status was fairly stable, nephrectomy was performed. Computed tomogram after nephrectomy revealed an embolus in the right pulmonary artery. Immediate embolectomy was scheduled. Tumor embolus was successfully removed under cardiopulmonary bypass. Fortunately, tumor pulmonary embolism did not lead to cardiopulmonary collapse in this case. However, tumorembolism is sometimes fatal. We should have considered the placement of a temporary IVC filter before surgery to prevent it.

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  Few reports have described anesthetic management for inclusion body myositis (IBM). A 76-year-old man suffering from dysphagia due to IBM underwent jejunostomy under general and epidural anesthesia. The trachea was intubated without using a muscle relaxant. The surgery was completed uneventfully. After confirming full recovery of spontaneous breathing, the trachea was extubated and he was transferred to the ward. On postoperative day 2, the patient developed aspiration pneumonia, which was successfully treated using antibiotics. Considering both this experience and previous case reports of inflammatory myopathies, we recommend using a non-depolarizing muscle relaxant during tracheal intubation. Intubation under stable conditions using these drugs may reduce the risk of aspiration during the procedure, thus minimizing the risk of postoperative pneumonia. Promotion of deep breathing and effective coughing by adequate postoperative analgesia, as well as prevention of aspiration pneumonia appear important in patients with IBM.

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  The effect site concentration of fentanyl during postoperative day 1 was simulated with a linear 3-compartment model, and an IV-PCA (intravenous patient-controlled analgesia) menu was created on the basis of the simulation result. The relation between postoperative effect site concentration and analgesic effect was then reviewed. The simulation indicates that the intravenous administration of 300 μg fentanyl accompanied with basal administration of 25 μg/h fentanyl, at 2h before the emergence, maintains a stable effect site concentration of 1.0 ng/ml in a 50-kg patient. The effect site concentrations of fentanyl, 1.4 ng/ml in the emergent period and 1.0 ng/ml in postoperative period, are useful in postoperative analgesia in non-abdominal surgery.

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  According to the Guidelines for Resuscitation 2010, all rescuers should minimize interruption of chest compressions (CC) during cardiopulmonary resuscitation (CPR), in order to maximize coronary and cerebral perfusion pressures. Ideally, tracheal intubation during CPR should be performed without interrupting CC. Impaired visibility of the glottis and passage through the glottis was considered to be the cause of difficulty performing tracheal intubation during CC. Various video or optical laryngoscopes have become clinically available and overcome these difficulties. Utility of non-sightline videolaryngoscopes for airway management during CC has been reported. From the viewpoint of ventilation during CC, various supraglottic devices such as laryngeal mask or laryngeal tube have been developed. Intubation with a supraglottic device may be useful for ventilation and subsequent intubation during CC. Furthermore, simulation training for not only advanced cardiac life support but also difficult and emergent airway management is important for anesthesiologists.

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