Targeted Temperature Management: Peltier's Element-Based Focal Brain Cooling Protects Penumbra Neurons from Progressive Damage in Experimental Cerebral Ischemia.

Targeted temperature management (TTM), or therapeutic hypothermia, is one of the most potent neuroprotective approaches after ischemic and traumatic brain injuries. TTM has been applied clinically with various methods, but effective achievement and maintenance of the target temperature remain challenging. Furthermore, timing of cooling and target body and brain temperature to optimize effectiveness for neuroprotection and to minimize side effects are yet to be standardized. Focal brain cooling is a potential strategy to minimize adverse effects of systemic TTM. In this study, we report on a focal brain cooling device for animals and its effectiveness of focal cooling in several animal models of ischemic cerebral stroke. A focal brain cooling device was constructed using a Peltier's element, a thermoelectric heat pump. The device was validated for its cooling ability, and optimal settings to induce an effective intracranial temperature were determined using male Sprague-Dawley rats. Transient and permanent middle cerebral artery occlusions were experimentally induced, and focal brain cooling was applied using the device varying the timing and duration of cooling. The stroke-induced infarct and edema volumes were evaluated from Nissl-stained cryosections. The focal brain cooling device was able to decrease and subsequently maintained cerebral hypothermia in free-moving rats without altering the core temperature. The device with validated intracranial temperatures produced neuroprotective effects in the acute phase of ischemic neural death, reperfusion injury, progressing damage to the penumbra, and edema formation. In conclusion, our validated focal cooling device enabled rapid and accurate cerebral TTM in rats. Using this device, we were able to test the neuroprotective effect of focal TTM in several pathological stages of cerebral ischemia, which warrants further studies to develop clinically feasible TTM procedures for patients with cerebral stroke.

Anesthetic Management of Pleurectomy/Decortication Under Differential Lung Ventilation.

A 64-year-old male (a building demolition worker) was diagnosed with malignant left-sided pleural mesothelioma, and left-sided pleurectomy/decortication was scheduled. Differential lung ventilation (DLV) was performed during the removal of the visceral pleura by connecting the affected lung to a ventilator and the healthy lung to an anesthesia machine, and then separately ventilating the left and right lungs. Anesthetic management using DLV was successfully established without causing significant changes in oxygenation or circulatory dynamics.

Anesthetic management during a cesarean section in a patient with cleidocranial dysplasia: a case report.

BACKGROUND: Cleidocranial dysplasia is a type of skeletal dysplasia, which is primarily characterized by delayed ossification of skeletal structures. It causes facial and oral abnormalities, resulting in difficult airway management and neuraxial anesthesia. CASE PRESENTATION: The patient was a 24-year-old primipara (height 138 cm, weight 42 kg) with a hypoplastic right clavicle, patent fontanelles, dental malalignment, and a high palate. She was diagnosed with cleidocranial dysplasia at birth, although gene examination has not been performed. The fetus was confirmed to have short limbs and large fontanelles during an examination performed at 28 weeks gestation, suspected to have cleidocranial dysplasia. The mother was scheduled for a cesarean section at 37 weeks and 1 day due to cephalopelvic disproportion. Preoperative radiography and magnetic resonance imaging revealed no vertebral and spinal abnormalities, which allowed combined spinal-epidural analgesia (CSEA) to be performed. The surgery was safely concluded under CSEA with no intraoperative respiratory or circulatory problems. CONCLUSIONS: Patients with cleidocranial dysplasia exhibit facial, oral abnormalities, and often vertebral abnormalities. Imaging assessments before neuraxial anesthesia and careful preparation for airway management are required.

HCN4 pacemaker channels attenuate the parasympathetic response and stabilize the spontaneous firing of the sinoatrial node.

KEY POINTS: The contribution of HCN4 pacemaker channels in the autonomic regulation of the sino-atrial node (SAN) has been a matter of debate. The transgenic overexpression of HCN4 did not induce tachycardia, but reduced heart rate variability, while the conditional knockdown of HCN4 gave rise to sinus arrhythmia. The response of the SAN to ß-adrenergic stimulation was not affected by overexpression or knockdown of HCN4 channels. When HCN4 channels were knocked down, the parasympathetic response examined by cervical vagus nerve stimulation (CVNS) was enhanced; the CVNS induced complete sinus pause. The overexpression of HCN4 attenuated bradycardia induced by CVNS only during ß-adrenergic stimulation. We concluded that HCN4 pacemaker channels stabilize the spontaneous firing by attenuating the parasympathetic response of the SAN. ABSTRACT: The heart rate is dynamically controlled by the sympathetic and parasympathetic nervous systems that regulate the sinoatrial node (SAN). HCN4 pacemaker channels are the well-known causative molecule of congenital sick sinus syndrome. Although HCN4 channels are activated by cAMP, the sympathetic response of the SAN was preserved in patients carrying loss-of-function mutations of the HCN4 gene. In order to clarify the contribution of HCN4 channels in the autonomic regulation of the SAN, we developed novel gain-of-function mutant mice in which the expression level of HCN4 channels could be reversibly changed from zero to ∼3 times that in wild-type mice, using tetracycline transactivator and the tetracycline responsive element. We recorded telemetric ECGs in freely moving conscious mice and analysed the heart rate variability. We also evaluated the response of the SAN to cervical vagus nerve stimulation (CVNS). The conditional overexpression of HCN4 did not induce tachycardia, but reduced heart rate variability. The HCN4 overexpression also attenuated bradycardia induced by the CVNS only during the ß-adrenergic stimulation. In contrast, the knockdown of HCN4 gave rise to sinus arrhythmia, and enhanced the parasympathetic response; complete sinus pause was induced by the CVNS. In vitro, we compared the effects of acetylcholine on the spontaneous action potentials of single pacemaker cells, and found that similar phenotypic changes were induced by genetic manipulation of HCN4 expression both in the presence and absence of ß-adrenergic stimulation. Our study suggests that HCN4 channels attenuate the vagal response of the SAN, and thereby stabilize the spontaneous firing of the SAN.

Insufficient Humidification of Respiratory Gases in Patients Who Are Undergoing Therapeutic Hypothermia at a Paediatric and Adult Intensive Care Unit.

For cooled newborn infants, humidifier settings for normothermic condition provide excessive gas humidity because absolute humidity at saturation is temperature-dependent. To assess humidification of respiratory gases in patients who underwent moderate therapeutic hypothermia at a paediatric/adult intensive care unit, 6 patients were studied over 9 times. Three humidifier settings, 37-default (chamber-outlet, 37°C; Y-piece, 40°C), 33.5-theoretical (chamber-outlet, 33.5°C; Y-piece, 36.5°C), and 33.5-adjusted (optimised setting to achieve saturated vapour at 33.5°C using feedback from a thermohygrometer), were tested. Y-piece gas temperature/humidity and the incidence of high (>40.6 mg/L) and low (<32.9 mg/L) humidity relative to the target level (36.6 mg/L) were assessed. Y-piece gas humidity was 32.0 (26.8-37.3), 22.7 (16.9-28.6), and 36.9 (35.5-38.3) mg/L {mean (95% confidence interval)} for 37-default setting, 33.5-theoretical setting, and 33.5-adjusted setting, respectively. High humidity was observed in 1 patient with 37-default setting, whereas low humidity was seen in 5 patients with 37-default setting and 8 patients with 33.5-theoretical setting. With 33.5-adjusted setting, inadequate Y-piece humidity was not observed. Potential risks of the default humidifier setting for insufficient respiratory gas humidification were highlighted in patients cooled at a paediatric/adult intensive care unit. Y-piece gas conditions can be controlled to the theoretically optimal level by adjusting the setting guided by Y-piece gas temperature/humidity.

Use of Normothermic Default Humidifier Settings Causes Excessive Humidification of Respiratory Gases During Therapeutic Hypothermia.

Adult patients frequently suffer from serious respiratory complications during therapeutic hypothermia. During therapeutic hypothermia, respiratory gases are humidified close to saturated vapor at 37°C (44 mg/L) despite that saturated vapor reduces considerably depending on temperature reduction. Condensation may cause serious adverse events, such as bronchial edema, mucosal dysfunction, and ventilator-associated pneumonia during cooling. To determine clinical variables associated with inadequate humidification of respiratory gases during cooling, humidity of inspiratory gases was measured in 42 cumulative newborn infants who underwent therapeutic hypothermia. Three humidifier settings of 37-default (chamber outlet, 37°C; distal circuit, 40°C), 33.5-theoretical (chamber outlet, 33.5°C; distal circuit, 36.5°C), and 33.5-adjusted (optimized setting to achieve 36.6 mg/L using feedback from a hygrometer) were tested to identify independent variables of excessively high humidity >40.7 mg/L and low humidity <32.9 mg/L. The mean (SD) humidity at the Y-piece was 39.2 (5.2), 33.3 (4.1), and 36.7 (1.2) mg/L for 37-default, 33.5-theoretical, and 33.5-adjusted, respectively. The incidence of excessive high humidity was 10.3% (37-default, 31.0%; 33.5-theoretical, 0.0%; 33.5-adjusted, 0.0%), which was positively associated with the use of a counter-flow humidifier (p < 0.001), 37-default (compared with 33.5-theoretical and 33.5-adjusted, both p < 0.001) and higher fraction of inspired oxygen (p = 0.003). The incidence of excessively low humidity was 17.5% (37-default, 7.1%; 33.5-theoretical, 45.2%; 33.5-adjusted, 0.0%), which was positively associated with the use of a pass-over humidifier and 33.5-theoretical (both p < 0.001). All patients who used a counter-flow humidifier achieved the target gas humidity at the Y-piece (36.6 ± 0.5 mg/L) required for 33.5-adjusted with 33.5-theoretical. During cooling, 37-default is associated with excessively high humidity, whereas 33.5-theoretical leads to excessively low humidity. Future studies are needed to assess whether a new regimen with optimized Y-piece temperature and humidity control reduces serious respiratory adverse events during cooling.

Intraperitoneal adipose tissue is strongly related to survival rate in a mouse cecal ligation and puncture model.

Cecal ligation and puncture (CLP) models exhibiting polymicrobial sepsis are considered as the gold standard in sepsis research. However, despite meticulous research being conducted in this field, only few treatment drugs are available, indicating that CLP sepsis models do not completely mimic human sepsis models. The greatest flaw in CLP models is abscess formation because the localization of inflammation caused by abscess formation increases the survival rate. Therefore, by resecting intraperitoneal adipose tissue, we developed a mouse CLP model wherein abscess formation was unlikely. Survival rates at 7 days postoperatively were compared using the Kaplan-Meier method for an intraperitoneal adipose tissue resection group (resection group, n=34), an intraperitoneal adipose tissue non-resection group (non-resection group, n=35) and a sham group (n=10). Results indicated that the survival rate was significantly higher in the non-resection group compared with the resection group. Intraperitoneal macroscopic findings in the non-resection group revealed the localization of inflammation caused by abscesses formation covered in adipose tissue. The survival rate for the sham group was 100%. Measurement of interleukin 6 (IL-6) indicated that during the 12 h after the creation of the CLP model, the median level of IL-6 was 1300 (552-3000) pg ml(-1) in the non-resection group (n=19) and 3000 (1224-8595) pg ml(-1) in the resection group (n=19). Meanwhile, for the sham group, IL-6 values were below measurement sensitivity in most cases (9/10 mice). Thus our results suggest that, in CLP models, intraperitoneal adipose tissue has an important role in abscess formation and is strongly related to the survival rate.

[A Case of Postoperative Paraplegia Caused by Idiopathic Spinal Cord Infarction following Hepatectomy under Both General and Epidural Anesthesia].

A 73-year-old woman (height : 155 cm, weight : 55 kg) was scheduled to undergo a laparotomic hepatectomy and radiofrequency ablation for hepatocellular carcinoma. Her medical history did not include any relevant conditions such as cardiovascular or neurological disorders. A thoracic epidural catheter was introduced at T8-9 before the induction of anesthesia with intravenous propofol. General anesthesia was maintained with the inhalation of oxygen, air, and desflurane, and the continuous infusion of remifentanil. Several intraoperative episodes of mild hypotension occurred, each of which was successfully treated with intravenous ephedrine, but otherwise her anesthetic course was uneventful, and she recovered from the anesthesia smoothly. Her postoperative pain was well controlled with continuous epidural infusion of levobupivacaine and fentanyl, and she could walk by herself on postoperative day (POD) 1. However, she suffered weakness in her lower extremities on POD2 and subsequently fell into complete paraplegia with sensory loss below the T4 level on POD3. A magnetic resonance imaging scan taken on POD4 showed an idiopathic spinal cord infarction (SCI) involving levels T1 through T4, although no epidural abnormalities, e.g., hematomas, were detected. Immediate treatment with methylprednisolone, ozagrel, and edaravone failed to resolve her symptoms. We suggest that it is of great importance to consider SCI as a differential diagnosis as soon as possible in cases of unanticipated postoperative paraplegia.

Ectopic automaticity induced in ventricular myocytes by transgenic overexpression of HCN2.

Hyperpolarization-activated cyclic nucleotide-gated channels (HCNs) are expressed in the ventricles of fetal hearts but are normally down-regulated as development progresses. In the hypertrophied heart, however, these channels are re-expressed and generate a hyperpolarization-activated, nonselective cation current (Ih), which evidence suggests may increase susceptibility to arrhythmia. To test this hypothesis, we generated and analyzed transgenic mice overexpressing HCN2 specifically in their hearts (HCN2-Tg). Under physiological conditions, HCN2-Tg mice exhibited no discernible abnormalities. After the application of isoproterenol (ISO), however, ECG recordings from HCN2-Tg mice showed intermittent atrioventricular dissociation followed by idioventricular rhythm. Consistent with this observation, 0.3 µmol/L ISO-induced spontaneous action potentials (SAPs) in 76% of HCN2-Tg ventricular myocytes. In the remaining 24%, ISO significantly depolarized the resting membrane potential (RMP), and the late repolarization phase of evoked action potentials (APs) was significantly longer than in WT myocytes. Analysis of membrane currents revealed that these differences are attributable to the Ih tail current. These findings suggest HCN2 channel activity reduces the repolarization reserve of the ventricular action potential and increases ectopic automaticity under pathological conditions such as excessive ß-adrenergic stimulation.

[Combined spinal-epidural anesthesia for a patient with HTLV-1 associated myelopathy].

An 81-year-old female with HTLV-1 associated myelopathy (HAM) was scheduled for transurethral lithotomy. She had had paresthesia and spastic paresis in the lower extremities for the past 15 years. The preoperative respiratory function test revealed a vital capacity of 1.3 l (58% of the predicted value). We selected combined spinal-epidural anesthesia (CSEA) for her to avoid postoperative respiratory complications due to general anesthesia. After placement of a thoracic epidural catheter, spinal anesthesia was achieved by administration of bupivacaine 7.5 mg, resulting in the sensory block level to T 6, five min later. The intraoperative blood pressure remained high at 150-200 mmHg, in spite of the administration of nicardipine. Postoperatively, neither the deterioration in the neurological findings of HAM nor the exacerbation of respiratory function was observed. The present report suggests that CSEA can be one of the choices of anesthesia for a patient with HAM.

Efficient transduction of 11 poly-arginine peptide in an ischemic lesion of mouse brain.

Direct intracellular delivery of intact proteins has been successfully achieved by tagging cell-penetrating peptide (CPP), which consists of short positively charged amino acids, such as 11 poly-arginine (11R); however, in vivo delivery of the proteins to the brain has remained challenging because it is unclear whether CPP would enable proteins to cross the blood-brain barrier (BBB). In this study, we conducted an in vivo kinetic study to investigate the efficiency of 11R-mediated peptide delivery in the normal and ischemic brain. The 11R was observed in the microvessels and neurons surrounding the microvessels throughout the brain 1 hour after systemic administration, but the signal of the peptide was faint after 2 hours. In a transient middle cerebral artery occlusion mouse model, 11R was markedly enhanced and remained detectable in the cells on the ipsilateral side for as long as 8 hours after administration compared with the contralateral side. These results suggest that 11R is capable of in vivo delivery to the brain by passing through the BBB. Furthermore, 11R-mediated protein transduction could be used for the delivery of therapeutic molecules in cerebral ischemia.

The use of amplitude-integrated electroencephalography combined with continuous conventional electroencephalography during therapeutic hypothermia for an infant with postnatal cardiac arrest.

INTRODUCTION: Amplitude-integrated electroencephalography (aEEG) has been employed in therapeutic hypothermia (TH) trials of neonates after perinatal hypoxic-ischemic encephalopathy (HIE). We present a case report involving the use of aEEG during TH with continuous conventional electroencephalography (cEEG) for an infant who experienced postnatal intraoperative cardiac arrest. CASE DESCRIPTION: A five-month-old infant developed cardiac arrest during operation. Return of spontaneous circulation was achieved after one hour of cardiopulmonary resuscitation. Therapeutic hypothermia was applied with neuromuscular blockades. During the TH, the brain function and seizures were monitored with aEEG, which can also display continuous cEEG. Intermittent and discrete seizures were detected on aEEG and confirmed with raw cEEG during the TH and rewarming periods. Several kinds of antiepileptic drugs (AEDs) were administered to manage seizures according to the findings of aEEG with cEEG. Seizures were controlled by the treatments, and she showed no clinical seizures after TH and AED discontinuation. DISCUSSION AND EVALUATION CONCLUSIONS: This case indicated the possibility that the use of aEEG with continuous cEEG for a postnatal infant after cardiac arrest was feasible to detect and assess seizures and the effects of antiepileptic therapy while undergoing TH.

A significant complication that occurred during insertion of dual guidewires into the right internal jugular vein for central venous catheterization.

We report a significant complication that occurred during double guidewire insertion. The first guidewire (GW1) was inserted under ultrasonographic guidance, whereas the second guidewire (GW2) was inserted by the landmark-based method. Subsequently, GW2 penetrated and entangled with GW1, which caused difficulty in removing both guidewires. A dilator was used to dilate the puncture site, allowing simultaneous removal of both guidewires with minimal invasion. The first guidewire was found to be pointing in a cranial direction, indicating the manner in which the second guidewire's puncture needle had penetrated it. Thus, when double cannulation is performed, guidewire position should be confirmed.

[Anesthetic management of a patient with Trousseau's syndrome and ovarian cancer who underwent gynecological surgery].

Trousseau's syndrome, a complex paraneoplastic disease, is characterized by the occurrence of thromboembolic disorders such as brain infarctions in patients with malignant neoplasms. We report the case of a 46-year-old woman with ovarian cancer who had suffered cerebral infarctions and presented with left hemiplegia, aphasia, and atypical genital bleeding. She suffered multiple right brain infarctions, a pulmonary embolism, a right renal infarction with bilateral hydronephrosis and deep venous thromboses and exhibited increased D-dimer and fibrinogen levels and so was administered heparin (10,000 U x day(-1)). She had no other underlying diseases such as coagulopathy, cardiovascular disease, collagen disease, or angiitis. Therefore, we were able to diagnose her with Trousseau's syndrome. She was scheduled to undergo total abdominal hysterectomy with bilateral oophorectomy, pelvic lymphadenectomies, and omentectomy. Preoperatively, an inferior vena cava filter was temporarily installed to prevent the development of further pulmonary thromboses. General anesthesia was uneventfully maintained by inhalation of oxygen, air, and sevoflurane and the continuous infusion of remifentanil whilst regional cerebral oxygen saturation and transesophageal echocardiography monitoring were performed. Postoperatively, she received heparin-based anticoagulant therapy (10,000 U x day(-1)) and did not exhibit bleeding diathesis or thrombosis. It is of great importance that anesthesiologists are aware of the thromboembolic status of patients with malignant neoplasms, especially those with gynecological tumors.

[A case of ventricular tachycardia that was probably caused by coronary artery spasm induced by pericardial manipulation].

We present a case of ventricular tachycardia (VT) that was probably caused by coronary artery spasm. A 74-year-old man was scheduled to undergo right lower lobectomy for lung cancer. Although he had never suffered from any episodes of ischemic heart disease, he had several risk factors for coronary artery disease (CAD); i. e., a history of smoking, a low high-density lipoprotein cholesterol level, and diabetes mellitus type 2. Anesthesia for one-lung ventilation was maintained by inhalation of sevoflurane (1-1.5%), the continuous intravenous infusion of remifentanil (0.1-0.15 µg x kg(-1) x min(-1)), and the intermittent administration of epidural (T4-5) 2% mepivacaine (4 ml) and 0.75% ropivacaine (5 ml). During manipulation of the pericardium, the patient's systolic blood pressure suddenly increased to 200 mmHg, followed by an ST elevation on his electrocardiogram. Despite the immediate infusion of nitroglycerin (1 mg), he developed non-sustained VT, lasting for about 30 seconds. Then, diltiazem (0.5 µg x kg(-1) x min(-1)) was continuously administered, and the infusion rate of remifentanil was increased to 0.3 µg x kg(-1) x min(-1). The patient recovered smoothly from anesthesia and his postoperative course was uneventful. Anesthesiologists should be aware of the possibility of coronary artery spasms induced by sudden modulation of the autonomic nervous system, particularly in patients who are at high risk of CAD.

[A case of a giant ovarian cyst anesthetized with the use of an inferior vena cava filter].

An intraperitoneal giant tumor can form deep venous thrombosis (DVT), leading to pulmonary embolism (PE) when it is removed. We report a case of a giant ovarian cystic tumor with possible DVT. A 52-year-old woman (149 cm in height, 85 kg in weight, and 150 cm in ventral girth) underwent the laparoscopic resection of the cyst. Preoperative angiography showed the obstruction of the inferior vena cava (IVC) just below the level of the right renal vein due to the compression by the tumor, and computed tomography suggested the existence of distal DVT. Anesthesia was induced with propofol and fentanyl, and the trachea was intubated using rocuronium. A permanent type IVC filter was placed near the obstruction site to prevent PE. Transesophageal echocardiography (TEE) was employed to detect the thrombotic echogram at the right atrium. Anesthesia was maintained with inhalation of sevoflurane and intravenous infusion of remifentanil. The content of the cyst (40.5 l) was suctioned slowly in about 50 min to avoid reexpansion pulmonary edema and circulatory collapse. Neither thrombotic echogram nor the acute decrease in end-tidal carbon dioxide pressure was observed throughout the anesthesia. Operation was performed uneventfully, and she recovered from anesthesia. We consider that IVC filters and TEE are useful to manage surgical patients with a huge ovarian cyst.

A case of delayed emergence from anesthesia caused by postoperative brain edema associated with unexpected cerebral venous sinus thrombosis.

Cerebral venous sinus thrombosis (CVST) is rare but displays various and often dramatic clinical symptoms. Few cases of CVST have been reported in the field of anesthesiology. We encountered an unexpected case of CVST that presented with delayed emergence from anesthesia after resection of a brain tumor. A 55-year-old man was scheduled for resection of an oligoastrocytoma in his right frontal lobe. After smooth induction of general anesthesia, anesthesia was maintained uneventfully for about 7 h with target-controlled infusion (TCI) of propofol and remifentanil, except for a seizure generated when the right anterior central gyrus was stimulated to allow motor evoked potential monitoring. Immediately after the cessation of TCI, spontaneous respiration was restored. However, the patient was unexpectedly comatose, and no response to painful stimuli or coughing during tracheal suctioning was observed. A computed tomogram taken 2 h after surgery showed diffuse brain edema, even though the neurosurgeons did not notice any cerebral swelling during closing of the dura mater. A magnetic resonance venogram revealed thromboses in the superior sagittal and straight sinuses. On the 9th postoperative day, the patient died without recovering consciousness or his brainstem reflexes. Anesthesiologists should be aware of CVST as a cause of delayed emergence from anesthesia after craniotomy.

[Anesthetic management of a patient with Rett syndrome associated with trismus and apnea attacks].

Rett syndrome (RTT) is a congenital neurological disorder associated with mutations in the gene encoding MECP2 on the X chromosome. An 18-year-old woman (150 cm in height and 29 kg in weight) had been diagnosed with RTT and showed myotonic trismus, frequent attacks of apnea, mental retardation, spastic paraplegia, scoliosis, and microcephalus with micrognathia. She was scheduled to undergo laparoscopic fundoplication and gastrostomy under general anesthesia. Nasal bronchofiberscopic intubation (BFI) was planned because difficult airway due to trismus and micrognathia was expected. Referring to the bispectral index (BIS), anesthesia was induced with intermittent intravenous thiopental (total 125 mg), resulting in successful opening of the mouth by 1.5 of a finger width and establishment of manual ventilation. Following intravenous administration of rocuronium (20 mg), oral BFI was easily accomplished despite Cormack grade III. Anesthesia was satisfactorily maintained with inhalation of sevoflurane (1.0-1.5%) and continuous infusion of remifentanil (0.1-0.2 microg x kg(-1) x min(-1)) with the BIS value ranging from 30 to 50. She recovered smoothly from anesthesia using sugammadex (50 mg). However, she immediately demonstrated trismus and an attack of apnea with shivering, which were successfully resolved by warming the body and intravenous fentanyl (50 microg bolus and subsequent infusion at a rate of 10 microg x hr(-1)). The postoperative course was uneventful. Characteristically, RTT shows an extremely wide range of neurological symptoms. Therefore, it is of great importance to respond to each of those symptoms during the perioperative management of patients with RTT.