A longitudinal study of auditory evoked field and language development in young children.

The relationship between language development in early childhood and the maturation of brain functions related to the human voice remains unclear. Because the development of the auditory system likely correlates with language development in young children, we investigated the relationship between the auditory evoked field (AEF) and language development using non-invasive child-customized magnetoencephalography (MEG) in a longitudinal design. Twenty typically developing children were recruited (aged 36-75 months old at the first measurement). These children were re-investigated 11-25 months after the first measurement. The AEF component P1m was examined to investigate the developmental changes in each participant's neural brain response to vocal stimuli. In addition, we examined the relationships between brain responses and language performance. P1m peak amplitude in response to vocal stimuli significantly increased in both hemispheres in the second measurement compared to the first measurement. However, no differences were observed in P1m latency. Notably, our results reveal that children with greater increases in P1m amplitude in the left hemisphere performed better on linguistic tests. Thus, our results indicate that P1m evoked by vocal stimuli is a neurophysiological marker for language development in young children. Additionally, MEG is a technique that can be used to investigate the maturation of the auditory cortex based on auditory evoked fields in young children. This study is the first to demonstrate a significant relationship between the development of the auditory processing system and the development of language abilities in young children.

Population pharmacokinetics of olprinone in patients undergoing cardiac surgery with cardiopulmonary bypass.

PURPOSE: Olprinone, a phosphodiesterase type III inhibitor, is a strong inotrope and vasodilator that does not increase oxygen consumption and is often used during weaning from cardiopulmonary bypass (CPB). To control the pharmacological effects of olprinone, pharmacokinetic information is essential; however, there is little published information on the pharmacokinetics of olprinone in a large population. Therefore, the purpose of this study was to determine olprinone pharmacokinetic parameters in a large population undergoing cardiac surgery with CPB. METHODS: Olprinone was infused at a rate of 0.2 µg/kg/min when weaning from CPB was started. Whole blood samples were periodically obtained to determine the olprinone concentrations using high-performance liquid chromatography. Measured olprinone concentrations were analyzed with a one-compartment model via a population approach. RESULTS: A total of 86 blood samples from 26 patients were used for pharmacokinetic analysis. The calculated clearance, volume of distribution (V(d)), and elimination half-life were 378 ml/min, 40.7 l, and 97.1 min, respectively. Olprinone clearance depended on weight and creatinine clearance, whereas V(d) depended only on weight. CONCLUSION: We investigated the pharmacokinetic parameters of olprinone in patients undergoing cardiac surgery with CPB. Olprinone clearance depended on weight and creatinine clearance, whereas V(d) depended only on weight. When olprinone is infused according to the recommended dosing regimen, it takes more than 60 min to reach the target concentration (20 ng/ml). However, there is a possibility that a lower concentration is sufficient for weaning from CPB in combination with a continuous infusion of dopamine.

The effect of hemodilution by cardiopulmonary bypass on protein binding of olprinone.

PURPOSE: Olprinone is a phosphodiesterase type III inhibitor that is often used to increase cardiac output after cardiopulmonary bypass (CPB). Hemodilution by CPB is likely to decrease total olprinone concentration, but it may also increase the free (unbound) concentration of olprinone due to reduced protein binding. The aim of this study was to investigate the effect of hemodilution on the protein binding of olprinone. METHODS: Eleven patients scheduled for elective cardiac surgery with CPB were enrolled in our study. Olprinone was continuously infused at a rate of 0.2 µg/kg/min from the time of the first surgical incision until the patient arrived at the recovery unit. Protein binding was evaluated twice, just before the start of CPB and at the beginning of withdrawal from CPB. Olprinone concentration and protein binding were determined with high-performance liquid chromatography and ultrafiltration methods, respectively. Olprinone protein binding was also evaluated in vitro. RESULTS: Olprinone protein binding to albumin was 63 % in vitro, but it did not bind to alpha-1 acid glycoprotein. Olprinone protein binding in patients before CPB was 81.5 ± 4.3 %, whereas protein binding at withdrawal from CPB was 63.3 ± 14.3 %. CONCLUSIONS: Unbound olprinone concentration increased by 20 % during CPB, which suggests that the pharmacological effects of olprinone might be enhanced during and after CPB. Close hemodynamic monitoring is necessary to control the effects of olprinone after CPB, because CPB alters olprinone's pharmacokinetics.

[Pharmacokinetics of anesthesia related drugs in patients with chronic kidney disease].

For anesthetic management, various kinds of drugs are administered to the patient. When unchanged drugs or their active metabolites are eliminated from the kidney, renal function has significant effects on the pharmacokinetics of the drugs. Generally, in such cases, drug or metabolite clearance shows a positive relation with glomerular filtration rate. When these drugs are administered to patients with renal impairment, drug concentrations are increased, prolonging the pharmacological effects or causing side-effects. In anesthesia related drugs, morphine, muscle relaxants, antibiotics and phosphodiesterase III inhibitors require special attention. Their dosages should be adjusted according to parameters of renal function such as creatinine clearance.

The incidence of hypotension during general anesthesia: a single-center study at a university hospital.

BACKGROUND: Although intraoperative hypotension (IOH) has been emerging as a serious concern during general anesthesia, the incidence of IOH has not been demonstrated clearly in the Japanese population. METHODS: This single-center retrospective study investigated the incidence and the characteristics of IOH in non-cardiac surgery at a university hospital. IOH was defined as at least one fall of MAP during general anesthesia, which was categorized into the following groups: mild (65 to < 75 mmHg), moderate (55 to < 65 mmHg), severe (45 to < 55 mmHg), and very severe (< 45 mmHg). The incidence of IOH was calculated as a percentage of the number of events to the total anesthesia cases. Logistic regression analysis was performed to examine factors affecting IOH. RESULTS: Eleven thousand two hundred ten cases out of 13,226 adult patients were included in the analysis. We found moderate to very severe hypotension occurred in 86.3% of the patients for at least 1 to 5 min, and 48.5% experienced severe or very severe hypotension. The results of the logistic regression analysis indicated female gender, vascular surgery, American Society of Anesthesiologists physical status classification (ASA-PS) 4 or 5 in emergency surgery, and the combination with the epidural block (EDB) were significant factors of IOH. CONCLUSIONS: IOH during general anesthesia was very frequent in the Japanese population. Female gender, vascular surgery, ASA-PA 4 or 5 in emergency surgery, and the combination with EDB were independent risk factors associated with IOH. However, the association with patient outcomes were not elucidated.

The use of a scented face mask in pediatric patients may facilitate mask acceptance before anesthesia induction.

Background: Scented face masks are commonly used during the induction phase of anesthesia. The present study investigated whether the use of a scented mask improved mask acceptance before the slow induction of anesthesia in pediatric patients. Methods: This prospective, randomized controlled trial enrolled patients aged 2-10 years who were scheduled to undergo surgery under general anesthesia. Patients were randomly assigned to either of regular unscented (control group) or scented (experimental group) face masks before anesthesia induction with a parent. The primary outcome was the mask acceptance score, rated on a validated 4-point from 1 point (not afraid; easily accepts the mask) to 4 points (afraid of a mask; crying or struggling). The secondary outcome was heart rate assessed by pulse oximetry in the pediatric ward before transfer to the operating room (OR), at the entrance to the OR, at the patient notification of mask fitting by the anesthesiologist, and after mask fitting. Results: Seventy-seven patients were accessed for eligibility, with 67 enrolled in the study: 33 in the experimental group and 34 in the control group. Mask acceptance was significantly greater among patients aged 2-3 years in the experimental than in the control group (p < 0.05). Conclusion: The use of a scented mask can improve mask acceptance before anesthesia induction with a parental presence in pediatric patients aged 2-3 years.Clinical Trial Registration: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000040819.

Lateralized theta wave connectivity and language performance in 2- to 5-year-old children.

Recent neuroimaging studies support the view that a left-lateralized brain network is crucial for language development in children. However, no previous studies have demonstrated a clear link between lateralized brain functional network and language performance in preschool children. Magnetoencephalography (MEG) is a noninvasive brain imaging technique and is a practical neuroimaging method for use in young children. MEG produces a reference-free signal, and is therefore an ideal tool to compute coherence between two distant cortical rhythms. In the present study, using a custom child-sized MEG system, we investigated brain networks while 78 right-handed preschool human children (32-64 months; 96% were 3-4 years old) listened to stories with moving images. The results indicated that left dominance of parietotemporal coherence in theta band activity (6-8 Hz) was specifically correlated with higher performance of language-related tasks, whereas this laterality was not correlated with nonverbal cognitive performance, chronological age, or head circumference. Power analyses did not reveal any specific frequencies that contributed to higher language performance. Our results suggest that it is not the left dominance in theta oscillation per se, but the left-dominant phase-locked connectivity via theta oscillation that contributes to the development of language ability in young children.

Language performance and auditory evoked fields in 2- to 5-year-old children.

Language development progresses at a dramatic rate in preschool children. As rapid temporal processing of speech signals is important in daily colloquial environments, we performed magnetoencephalography (MEG) to investigate the linkage between speech-evoked responses during rapid-rate stimulus presentation (interstimulus interval < 1 s) and language performance in 2- to 5-year-old children (n = 59). Our results indicated that syllables with this short stimulus interval evoked detectable P50m, but not N100m, in most participants, indicating a marked influence of longer neuronal refractory period for stimulation. The results of equivalent dipole estimation showed that the intensity of the P50m component in the left hemisphere was positively correlated with language performance (conceptual inference ability). The observed positive correlations were suggested to reflect the maturation of synaptic organisation or axonal maturation and myelination underlying the acquisition of linguistic abilities. The present study is among the first to use MEG to study brain maturation pertaining to language abilities in preschool children.

Awareness during anesthesia: the results of a questionnaire survey in Japan.

PURPOSE: We planned a survey to evaluate the current incidence and risk factors of intraoperative awareness. METHODS: A questionnaire survey was conducted via the Internet. The survey was designed to obtain information regarding cases involving intraoperative awareness in 2008. RESULTS: A total of 172 anesthesiologists answered the survey. The total number of reported anesthetic cases was 85,156. Twenty-four cases of definite or possible awareness were reported by 21 anesthesiologists, of which 14 were cases of definite awareness and ten of possible awareness. The incidence of awareness, including possible awareness, was 0.028%. Propofol was used in 21 cases, sevoflurane in two, and a high dose of fentanyl in one. Bispectral index (BIS) monitoring was used in seven cases (29%). Sixteen patients (67%) were <50 years old, six (26%) were men, and 17 (74%) were women. As the type of surgery, three cases (13%) involved gynecological surgeries and seven (30%) involved cervicofacial surgeries. During surgery, the memory at postural change was preserved in two cases. CONCLUSION: The most surprising finding of this study is that total intravenous anesthesia (TIVA) was used in 21 of the 24 (88%) cases of definite and possible awareness. Although the incidence of intraoperative awareness was compatible with the previous studies, meticulous care should be taken when anesthesia is performed by TIVA for high-risk patients. The results of this survey should be verified, as well as further continuous survey and prospective study, because this study was performed by an anonymous questionnaire survey conducted over only 1-year period.

[Patient with posterior reversible encephalopathy syndrome with prolonged disturbance of consciousness and convulsion after cerebral aneurysm surgery].

A 73-year-old patient developed convulsion and prolonged disturbance of consciousness after clipping surgery for unruptured cerebral aneurysm. The patient's consciousness improved four days after surgery, and radiological findings suggested posterior reversible encephalopathy syndrome (PRES). The cause of PRES is thought to be dysfunction of blood brain barrier by a sudden increase in blood pressure. In case of unexplained convulsion and decreased level of consciousness, PRES should be considered with radiographic examinations including CT and MRI.

Intravenous infusion of rocuronium bromide prolongs emergence from propofol anesthesia in rats.

BACKGROUND: Neuromuscular blocking agents induce muscle paralysis via the prevention of synaptic transmission at the neuromuscular junction and may have additional effects at other sites of action. With regard to potential effects of neuromuscular blocking agents on the central nervous system, a definitive view has not been established. We investigated whether intravenous infusion of rocuronium bromide affects the emergence from propofol anesthesia. METHODS: Using an in vivo rat model, we performed propofol infusion for 60 minutes, along with rocuronium bromide at various infusion rates or normal saline. Sugammadex or normal saline was injected at the end of the infusion period, and we evaluated the time to emergence from propofol anesthesia. We also examined the neuromuscular blocking, circulatory, and respiratory properties of propofol infusion along with rocuronium bromide infusion to ascertain possible factors affecting emergence. RESULTS: Intravenous infusion of rocuronium bromide dose-dependently increased the time to emergence from propofol anesthesia. Sugammadex administered after propofol infusion not containing rocuronium bromide did not affect the time to emergence. Mean arterial pressure, heart rate, partial pressures of oxygen and carbon dioxide, and pH were not affected by rocuronium bromide infusion. Neuromuscular blockade induced by rocuronium bromide, even at the greatest infusion rate in the emergence experiment, was rapidly antagonized by sugammadex. CONCLUSIONS: These results suggest that intravenous infusion of rocuronium bromide dose-dependently delays the emergence from propofol anesthesia in rats. Future studies, such as detection of rocuronium in the cerebrospinal fluid or central nervous system, electrophysiologic studies, microinjection of sugammadex into the brain, etc., are necessary to determine the mechanism of this effect.

[Anesthetic management of a patient with acquired factor V inhibitor].

A 74-year-old man was scheduled for laparoscopic low anterior resection of rectal cancer. Preoperative blood coagulation test showed his prothrombin time (PT) and activated partial thromboplastin time (APTT) remarkably prolonged. However, he experienced only slight epistaxis. Further examination suggested the presence of acquired factor V inhibitor. Plasmapheresis was carried out before surgery to eradicate inhibitors, but improvement of PT and APTT was temporary. We prepared platelet transfusion and recombinant activated factor VII (rFVIIa) for acute intraoperative bleeding, but there were no abnormal episodes during the surgery. On postoperative day 15, the patient suddenly passed blood in his stool, and received platelet transfusion. For the majority of patients with acquired factor V inhibitor, bleeding is usually mild, but fatal bleeding complications have also been reported. Platelet transfusion was effective in the patient described here.

[Intravenous thrombus detected during central venous catheterization under ultrasonic guidance].

A bedridden 88-year-old woman with cerebral infarction was scheduled for central venous catheterization through the right internal jugular vein under ultrasonic guidance. She had received central venous catheterization through the right internal jugular vein one month before, but the catheter had been removed nine days previously because of catheter infection. The right internal jugular vein was punctured under ultrasonic guidance, but blood regurgitation was not observed. Further observation with ultrasonography showed a high-echoic region in the internal jugular vein, and no blood flow was observed at the vein by Doppler ultrasound examination. In addition, the vein was not compressed by the probe of the ultrasonic device. Intravenous thrombus was suspected, and the procedure was stopped. Risk factors for intravenous thrombus include advanced age, cerebral infarction, bedridden patient, and catheter-related infection. When attempting recatheterization through the same vein for patients with these risk factors, especially catheter-related infection, attention should be paid to the possibility of intravenous thrombus. In cases in which intravenous thrombus is suspected, catheterization should be attempted through another vein.

[Anesthetic management of a patient with severe combined pulmonary disease under epidural anesthesia with spontaneous respiration].

A 74-year-old man with gastric cancer was complicated with abdominal aortic aneurysm. A two-stage operation was scheduled (repair of abdominal aortic aneurysm and subsequent gastrectomy). He also had severe chronic obstructive pulmonary disease (COPD). We planned to maintain spontaneous breathing during operations under epidural anesthesia and light general anesthesia. For the first surgery, two epidural catheters were placed at T1-2 and T7-8 on the day before surgery. After establishing epidural anesthesia, general anesthesia was induced and maintained with midazolam, fentanyl and sevoflurane, but without muscle relaxants under BIS monitoring. Ropivacaine solution 0.375% was infused through an epidural catheter to provide analgesia, and spontaneous breathing was kept throughout the procedure. Surgery lasted 4 hours and 50 minutes, and patient recovered without complications. Forty days after the first surgery, the second operation was scheduled. Anesthetic management was almost the same as in the first one, except for the use of dexmedetomizine rather than sevoflurane. In both operations, sufficient analgesia was provided with epidural anesthesia, and the surgeons rated muscle relaxation as satisfactory. No respiratory complications developed postoperatively. Maintaining spontaneous breathing during abdominal surgery using epidural anesthesia and light general anesthesia is a good option for COPD patients.

[Hypoxemia during cesarean section due to massive pleural effusion in a patient with preeclampsia].

We report hypoxemia during cesarean section in a 33-year-old woman with preeclampsia. She developed generalized body weight increase, severe proteinuria and decrease of platelets at week 33 of gestation. Cesarean section was scheduled under general anesthesia. The patient did not complain of dyspnea preoperatively. After induction of general anesthesia, arterial oxygen saturation decreased from 99 to 88%. Massive left pleural effusion was detected and chest drainage was performed, and oxygenation was improved. Accumulation of pleural effusion tends to be over-looked because many parturients with pleural effusion do not complain of dyspnea. Physicians should pay attention to pleural effusion in parturients, especially those with risk factors such as preeclampsia, generalized body weight increase and administration of beta stimulant.