Hideki Miyao

Neonatal Exposure to Sevoflurane Induces Abnormal Social Behaviors and Deficits in Fear Conditioning in Mice

Background:Neonatal exposure to anesthetics that block N-methyl-d-aspartate receptors and/or hyperactivate &ggr;-aminobutyric acid type A receptor has been shown to cause neuronal degeneration in the developing brain, leading to functional deficits later in adulthood. The authors investigated whether exposure of neonatal mice to inhaled sevoflurane causes deficits in social behavior as well as learning disabilities. Methods:Six-day-old C57BL/6 mice were exposed to 3% sevoflurane for 6 h. Activated cleaved caspase-3 immunohistochemical staining was used for detection of apoptosis. Cognitive functions were tested by pavlovian conditioned fear test. Social behavior was tested by social recognition and interaction tests. Results:Neonatal exposure to sevoflurane significantly increased the number of apoptotic cells in the brain immediately after anesthesia. It caused persistent learning deficits later in adulthood as evidenced by decreased freezing response in both contextual and cued fear conditioning. The social recognition test demonstrated that mice with neonatal exposure to sevoflurane did not develop social memory. Furthermore, these mice showed decreased interactions with a social target compared with controls in the social interaction test, indicating a social interaction deficit. The authors did not attribute these abnormalities in social behavior to impairments of general interest in novelty or olfactory sensation, because they did not detect significant differences in the test for novel inanimate object interaction or for olfaction. Conclusions:This study shows that exposure of neonatal mice to inhaled sevoflurane could cause not only learning deficits but also abnormal social behaviors resembling autism spectrum disorder.

Electron microscopic evaluations of clot morphology during thrombelastography

In this study, we characterized clot morphology with a scanning electron microscope (SEM) at time points corresponding to the commonly used thrombelastography (TEG®) variables, illustrating the correlation of the physical clot formation with TEG® tracings. The first channel of the TEG® analyzer was used to obtain the tracings of clot formation, while the sub-samples for the SEM were obtained from the second TEG® channel. Different types of samples were examined, including whole blood, abciximab-treated whole blood, platelet-rich plasma (PRP), and abciximab-treated PRP. The SEM images were obtained at reaction time, different amplitudes (5–30 mm), maximum amplitude (MA), and at amplitude 60 min after MA. In the whole blood, coarse fibrin and activated platelets were observed at reaction time and fibrin strands progressively became more solid and intertwined at amplitude 10 mm and thereafter. Red blood cells were surrounded with fibrin strands at amplitude 30 mm and were tightly packed by fibrin strands at MA. In abciximab-treated whole blood, red blood cell shape was maintained at MA. The process of fibrin formation and platelet activation was also examined in PRP. Abciximab did not block platelet shape change, although the blockage of fibrin binding to platelets was shown on the TEG® analyzer. In summary, we have shown structural changes of the forming clot in relation to TEG® variables.

Relative humidity, not absolute humidity, is of great importance when using a humidifier with a heating wire

ObjectivesSince the introduction of a humidifier with a heating wire, we have frequently experienced severe upper airway obstruction from consolidation of secretions, previously unencountered when a humidifier without a heating wire was used. Such problems led to the suspicion that the heating wire incorporated into the breathing circuit of the heated humidifier might be the cause. Therefore, we scheduled an experiment to assess the hypothesis that relative humidity, rather than absolute humidity, is a dominant factor in the case of drying secretions in the upper airway when using such a humidifier. DesignThree clinical case reports and an experiment with a tracheal model. SettingIntensive care units at Saitama Medical Center, Saitama Medical School, Saitama, Japan. PatientsThree intubated patients. Measurements and Main ResultsAn experiment with a tracheal model showed that gas with a higher temperature and lower relative humidity (35dEC, 48%) deprived the tracheal model of significantly more water (5.9 ±PT 0.2 [SD] g) than gas with a lower temperature and higher relative humidity (24°, 87%) (2.9 ±PT 0.4 g; p < .01), even though the gases contained the same amount of water vapor (19 mg H2O/L) minus the same absolute humidity. ConclusionsA heated humidifier with a heating wire incorporated into the breathing circuit may be dangerous when only temperature is monitored and controlled. Relative humidity, rather than absolute humidity, is a dominant factor in the case of drying secretions in the upper airway when using such a humidifier. (Crit Care Med 1992; 20:674–679)

Delayed respiratory depression associated with 0.15 mg intrathecal morphine for cesarean section: a review of 1915 cases

PurposeA low dose of morphine, given intrathecally is an effective postoperative analgesic technique and is widely used in cesarean section. Delayed respiratory depression is the most feared side effect of this technique. However, this side effect has not been thoroughly reported in the obstetric population. The aim of this study was to describe respiratory depression associated with intrathecal morphine in postcesarean women, and to estimate its incidence.MethodsWe retrospectively reviewed the obstetric anesthesia database at our institution from April 2000 to December 2006. Patients who were given 0.15 mg intrathecal morphine for cesarean section were identified. From this group, we identified patients who developed bradypnea (respiratory rate ≤ 10 breaths·min−1) within 24 h after the intrathecal injection.ResultsOf 1915 women given 0.15 mg intrathecal morphine for postcesarean analgesia, 6 patients exhibited bradypnea within 24 h after the injection of morphine. Four of these 6 patients developed mild respiratory depression, which was treated with supplemental oxygen and/or encouragement of breathing. One patient had severe respiratory depression, and repeated episodes of oxygen desaturation below 90% and 30-s apneas were noted. Naloxone was required for this patient. One woman had obstructive sleep apnea which was not associated with the intrathecal morphine.ConclusionOf 1915 patients, 5 women (0.26%) developed bradypnea associated with 0.15 mg intrathecal morphine. The incidence of severe bradypnea requiring naloxone was 1/1915 (0.052%).

Determination of the standard value of circulating blood volume during anesthesia using pulse dye-densitometry: a multicenter study in Japan.

PurposeThe standard value for circulating blood volume (BV) during anesthesia was determined by a multicenter study in Japan. The significance of BV on the reduction of blood pressure after the induction of anesthesia was also examined.MethodsThe study included 184 patients from eight university hospitals. After the induction of anesthesia, pulse dye-densitometry was performed according to a uniform protocol. Factors contributing to reduced blood pressure after induction of anesthesia were examined by multiple logistic regression analysis.ResultsThe mean and standard deviation of BV was 80.0 ± 13.9 ml·kg−1; for females and 84.2 ± 15.3 ml·kg−1 for males (P > 0.05). There was no age difference in terms of BV. After adjusting for the effects of height, weight, and age, the factors predisposing to a reduction in blood pressure of >20 mmHg after induction of anesthesia were found to be age (P < 0.01) and BV (ml·kg−1) ( P < 0.001).ConclusionWe determined the BV of anesthetized patients before surgery in Japan using pulse dye-densitometry. It is suggested that age is not a factor regarding BV, and that blood pressure tends to be reduced in hypovolemic patients after induction of anesthesia.

Cp50 of propofol for laryngeal mask airway insertion using predicted concentrations with and without nitrous oxide

This study sought to determine the predicted Cp50 of propofol required for laryngeal mask airway insertion (Cp50LMA) and to investigate whether nitrous oxide reduces these required concentrations. Using target‐controlled infusion and incorporating the standard Diprifusor™ pharmacokinetic model, 46 unpremedicated patients were randomly assigned to one of two groups. The patients received either 40% oxygen in air (control group: n = 23), or 60% nitrous oxide in oxygen (nitrous oxide group: n = 23). The target concentration for each patient was determined using the up and down method. Following equilibration between the predetermined blood and effect site concentrations, had been established for > 10 min, laryngeal mask airway insertion was attempted without neuromuscular relaxants. The data were analysed using a probit analysis to obtain Cp50LMA levels. The values for Cp50LMA were 3.24 µg.ml−1 in the control group and 1.93 µg.ml−1 in the nitrous oxide group.

A Method for Studying Interaction Between Non-Deporalizing Neuromuscular Blockers and Other Drugs in Vivo

In view of clinical set, there are not so many methods for studying interactions between non-deporalizing neuromuscular blockers and other drugs. We schemed out a new methods for studying the interactions mentioned above.