Faculty Profiles - HIGUCHI Hitoshi

Remifentanil suppresses increase in interleukin-6 mRNA in the brain by inhibiting cyclic AMP synthesis Reviewed

Shigeru Maeda, Tsugunobu Andoh, Rieko Onishi, Yumiko Tomoyasu, Hitoshi Higuchi, Takuya Miyawaki

Journal of Anesthesia 32 ( 5 ) 731 - 739 2018.8

The effect of Tmem135 overexpression on the mouse heart. Reviewed

Lewis SA, Takimoto T, Mehrvar S, Higuchi H, Doebley AL, Stokes G, Sheibani N, Ikeda S, Ranji M, Ikeda A.

PLoS One 13 ( 8 ) e0201986 2018.8

In vitro changes in the proportion of protein-unbound-free propofol induced by valproate Reviewed

Minako Ishii-Maruhama, Hitoshi Higuchi, Mai Nakanou, Yuka Honda-Wakasugi, Akiko Yabuki-Kawase, Shigeru Maeda, Takuya Miyawaki

Journal of Anesthesia 32 ( 5 ) 688 - 693 2018.7

Intellectual disability is a risk factor for delayed emergence from total intravenous anaesthesia Reviewed

H. Higuchi, S. Maeda, M. Ishii-Maruhama, Y. Honda-Wakasugi, A. Yabuki-Kawase, T. Miyawaki

Journal of Intellectual Disability Research 62 ( 3 ) 217 - 224 2017.11

Capnography prevents hypoxia during sedation for dental treatment: A randomized controlled trial Reviewed

K. Takaya, H. Higuchi, M. Ishii-Maruhama, A. Yabuki-Kawase, Y. Honda, Y. Tomoyasu, S. Maeda, T. Miyawaki

JDR Clinical and Translational Research 2 ( 2 ) 158 - 167 2017.4

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

Intravenous sedation is useful for dental treatment in patients with intellectual disabilities. However, it is often necessary to manage such patients with deep sedation because their cooperation cannot be obtained. During deep sedation, undetected hypoventilation can lead to severe complications, such as hypoxia. Recently, capnographic monitoring has been advocated as a useful technique for preventing hypoxia during sedation. This randomized control trial evaluated whether the use of capnography reduces the incidence of hypoxia during the deep sedation of patients for dental treatment. This study involved patients with intellectual disabilities who underwent dental treatment under sedation. The subjects were randomized to the intervention group (I-group) or control group (C-group). All of the patients underwent routine monitoring, as well as bispectral index (BIS) and capnographic monitoring; however, only an independent observer had access to the patients’ capnographic data during the dental procedures. Sedation was maintained at a BIS of 50 to 70 by administration of propofol. In the I-group, the independent observer signaled to the dental anesthesiologist if the capnogram indicated that the patient had been suffering from alveolar hypoventilation or apnea for >15 s. In the C-group, the observer signaled to the dental anesthesiologist if the capnogram indicated that the patient had been suffering from alveolar hypoventilation or apnea for >60 s. In both groups, the dental anesthesiologists responded to the signals using appropriate airway management strategies. The primary endpoint of this study was the incidence of hypoxia during dental treatment, which was defined as oxygen saturation of <95%. Hypoxemic episodes occurred in 13.4% and 34.8% of cases in the I-group and C-group, respectively. The incidence of hypoxia was significantly lower in the I-group. These results suggest that capnographic monitoring during deep sedation for dental treatment prevents hypoxemic episodes by allowing the early detection of hypoventilation. Knowledge Transfer Statement: This is the first randomized controlled trial to examine whether the use of capnography reduces the incidence of hypoxia during deep sedation for dental treatment. The findings of this study can be used by clinicians to aid decision-making regarding dental sedation standards at individual clinics. Moreover, they can be used as high-level evidence during the production or updating of clinical guidelines for dental sedation by leading associations.

DOI： 10.1177/2380084416674670

Clinical Analysis of Analgesics and Steroids Use for Extraction of Teeth in Patients with Intellectual Disability Under General Anesthesia. Reviewed International journal

Shigeru Maeda, Yuka Honda, Hiroshi Tanimura, Yumiko Tomoyasu, Hitoshi Higuchi, Naomichi Murata, Masahiko Egusa, Takuya Miyawaki

The open dentistry journal 11 181 - 186 2017.3

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The extraction of lower wisdom teeth is often performed under general anesthesia in patients with intellectual disabilities. However, the choice of analgesics has not yet been investigated. OBJECTIVE: To analyze the use of analgesics during general anesthesia for extraction including lower wisdom teeth in patients with intellectual disabilities. METHODS: This research is a retrospective observational study. The study population was composed of all patients presenting for extraction of lower wisdom teeth under ambulatory general anesthesia in the clinic of Special Needs Dentistry in Okayama University Hospital from April 2011 to March 2016. The distribution of the combination of analgesics and the relationship between the use of analgesics and the type of extraction were investigated. RESULTS: One hundred and twelve cases were enrolled in this study. Intravenous injections of flurbiprofen, acetaminophen and betamethasone were used in 96 (85.7%), 12 (10.7%) and 26 cases (23.2%), respectively. Flurbiprofen is a non-steroid anti-inflammatory drugs (NSAIDs). Acetaminophen is an old analgesic, but an injection of acetaminophen is new, which was released in 2013 in Japan. And betamethasone is not an analgesic, but a steroid. Betamethasone was used in combination with other analgesics, and was used at a higher dose in a case in which four wisdom teeth were extracted. CONCLUSION: Flurbiprofen was the main analgesic used for extraction of wisdom teeth under general anesthesia in patients with intellectual disabilities. Betamethasone was used to support flurbiprofen or acetaminophen for extractions of multiple wisdom teeth, with the aim of controlling swelling rather than relieving pain.

DOI： 10.2174/1874210601711010181

Effect of Intravenous Patient-controlled Analgesia (IV-PCA) on Postoperative Pain in Patients Undergoing Surgery for Oral and Maxillofacial Tumors Reviewed

日本歯科麻酔学会雑誌 45 ( 1 ) 17 - 22 2017.1

Anesthetic management of a child with diamond-Blackfan Anemia and cyanotic congenital heart disease undergoing cleft lip repair

Yukiko Nishioka, Hiroshi Tanimura, Rieko Onishi, Yuka Honda-Wakasugi, Akiko Yabuki-Kawase, Hitoshi Higuchi, Shigeru Maeda, Takuya Miyawaki

Journal of Japanese Dental Society of Anesthesiology 45 ( 5 ) 669 - 671 2017

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Japanese Dental Society of Anesthesiology

Diamond-Blackfan anemia (DBA) is a rare congenital form of pure red cell aplasia that is often complicated by congenital anomalies such as craniofacial anomalies and heart disease. We report a case of cleft lip repair performed under general anesthesia in a child with DBA. The patient was a male aged 12 years old, 95.8cm in height, and 12.8 kg in body weight He had anemia, a double-outlet right ventricle (DORV), and coarctation of the aorta (CoA). He had been treated with the administration of prednisolone and red blood cell transfusion for the anemia. Because steroid therapy increases the risk of infection, he was unable to undergo a radical operation for DORV. He exhibited cyanosis with an SpO2 of 75% under 2//min oxygen, and we considered tracheal intubation to be difficult because of the craniofacial anomaly. Before the induction of anesthesia, his SpO2 was 76%. Anesthesia was induced with thiopental. Because tracheal intubation was difficult, we performed oral intubation using a video laryngoscope. Anesthesia was maintained with oxygen, air, sevoflurane, and fentanyL To prevent infective endocarditis (IE), we administered ampicillin just before the operation, and 2% lidocaine with 1/240, 000 adrenalin was used for local anesthesia Under mechanical ventilation with the pressure mode, the FIO2 was kept at 0.5 to maintain the SpO2 at around 75%. In the present case, we needed to manage respiration and circulation because of cyanotic congenital heart disease, to take measures because of a difficult tracheal intubation, to prevent IE, and to prepare for red blood cell transfusion for anemia As a result, we were able to manage the general condition of a child with Diamond-Blackfan anemia and cyanotic congenital heart disease during general anesthesia safely without any complications.

Mouse Tmem135 mutation reveals a mechanism involving mitochondrial dynamics that leads to age-dependent retinal pathologies Reviewed

Wei-Hua Lee, Hitoshi Higuchi, Sakae Ikeda, Erica L Macke, Tetsuya Takimoto, Bikash R Pattnaik, Che Liu, Li-Fang Chu, Sandra M Siepka, Kathleen J Krentz, C Dustin Rubinstein, Robert F Kalejta, James A Thomson, Robert F Mullins, Joseph S Takahashi, Lawrence H Pinto, Akihiro Ikeda

eLife 5 e19264 2016.11

Female Patients Require a Higher Propofol Infusion Rate for Sedation. Reviewed International journal

Shigeru Maeda, Yumiko Tomoyasu, Hitoshi Higuchi, Yuka Honda, Minako Ishii-Maruhama, Takuya Miyawaki

Anesthesia progress 63 ( 2 ) 67 - 70 2016.8

Language：English Publishing type：Research paper (scientific journal)

Sedation may minimize physiologic and behavioral stress responses. In our facility, the infusion rate of propofol is adjusted according to the bispectral index (BIS) in all cases of implant-related surgery; multivariate analysis of retrospective data enabled us to extract independent factors that affect the dose of propofol in sedation that are considered useful indicators for achieving adequate sedation. The study population comprised all patients undergoing implant-related surgery under intravenous sedation in Okayama University Hospital from April 2009 to March 2013. The infusion rate of propofol was adjusted to maintain the BIS value at 70-80. The outcome was the average infusion rate of propofol, and potential predictor variables were age, sex, body weight, treatment time, and amount of midazolam. Independent variables that affected the average infusion rate of propofol were extracted with multiple regression analysis. One hundred twenty-five subjects were enrolled. In the multiple regression analysis, female sex was shown to be significantly associated with a higher average infusion rate of propofol. Females may require a higher infusion rate of propofol than males to achieve adequate sedation while undergoing implant-related surgery.

DOI： 10.2344/0003-3006-63.2.67

Effect of a low dose of midazolam on high blood pressure in dental patients: A randomised, double-blind, placebo-controlled, two-centre study

Yoshihisa Watanabe, Hitoshi Higuchi, Minako Ishii-Maruhama, Yuka Honda, Akiko Yabuki-Kawase, Ayaka Yamane-Hirano, Yumiko Tomoyasu, Shigeru Maeda, Takuya Miyawaki

British Journal of Oral and Maxillofacial Surgery 54 ( 4 ) 443 - 448 2016.5

Language：English Publishing type：Research paper (international conference proceedings) Publisher：Churchill Livingstone

Some patients have transient hypertension before dental treatment as a result of anxiety and stress. Midazolam is an anxiolytic, and thought to be effective for the management of this sort of transient hypertension. We have evaluated in a randomised, controlled trial whether a low dose of midazolam can lower blood pressure in dental patients to an acceptable level without excessive sedation. Suitable patients were randomised to be given midazolam (trial group) or physiological saline (control group) intravenously. Blood pressure, heart rate, degree of anxiety, and amount of sedation were measured before and after injection. After injection, blood pressure in the trial group significantly decreased to clinically acceptable levels compared with controls. The degree of anxiety in the trial group was also significantly less than that in the control group, but there were no significant differences in sedation. These results suggest that injection of a low dose of midazolam stabilises the blood pressure of dental patients with transient hypertension.

DOI： 10.1016/j.bjoms.2016.02.006

知的障害を有する肥満患者の静脈内鎮静法下歯科治療における経鼻高流量酸素供給システム (Optiflow) の使用経験 Reviewed

大西梨恵子, 樋口仁, 川瀬明子, 丸濱美菜子, 本田優花, 前田茂, 宮脇卓也

日本歯科麻酔学会雑誌 44 ( 2 ) 207 - 209 2016.4

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：(一社)日本歯科麻酔学会

症例は40歳男性で、重度の知的障害を有しておりコミュニケーションが不可能であったため、通常の方法では歯科治療のみならず診察も行うことができなかった。半年に1度の頻度で静脈内鎮静法下での定期検診を受けていた。静脈路確保が困難であることから、麻酔前投薬としてジュースにミダゾラムを混ぜて内服させた。入眠後は舌根沈下することが多かったため、入眠直後より経鼻エアウェイを挿入するとともに経鼻カニューラから酸素を投与したが頻繁にSpO2は90〜95%になった。過去の経過を踏まえ、静脈内鎮静法中の低酸素血症を予防するために、経鼻高流量酸素供給システム(Optiflow)を用いることを計画した。歯科処置中は気道確保を容易に行うことができ、気道閉塞および呼吸状態の異常を認めることはなく、経鼻エアウェイを使用する必要もなかった。歯科治療中のSpO2は終始98〜99%で推移した。プロポフォール投与終了後60分で覚醒し、ミダゾラム投与2時間45分後に帰宅した。術後合併症はなかった。

Effect of carbamazepine or phenytoin therapy on blood level of intravenously administered midazolam : a prospective cohort study Reviewed

Effect of a low dose of midazolam on high blood pressure indental patients: a randomised, double-blind,placebo-controlled, two-centre study Reviewed

Yoshihisa Watanabe, Hitoshi Higuchi, Minako Ishii-Maruhama, Yuka Honda, Akiko Yabuki-Kawase, Ayaka Yamane-Hirano, Yumiko Tomoyasu, Shigeru Maeda,Takuya Miyawaki

British Journal of Oral and Maxillofacial Surgery 54 ( 4 ) 443 - 448 2016.3

Journal of anesthesia 30 ( 1 ) 166 - 169 2016.2

Airway management using a nasal high flow system (Optiflow™) during intravenous sedation for dental treatment in an obese patient with intellectual disability

Rieko Onishi, Hitoshi Higuchi, Akiko Kawase, Minako Maruhama, Yuka Honda, Shigeru Maeda, Takuya Miyawaki

Journal of Japanese Dental Society of Anesthesiology 44 ( 2 ) 207 - 209 2016

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Japanese Dental Society of Anesthesiology

Intravenous sedation (IVS) is useful for the dental treatment of patients with intellectual disability (ID). However, in obese patients, difficulties in airway management can easily lead to oxygen desaturation. Nasal high-flow systems (NHFS) are a new type of device that can supply oxygen at a high flow rate. Several recent studies have shown that the use of an NHFS is very effective for preventing oxygen desaturation, and we have used an NHFS for airway management during IVS for a dental procedure in a patient with severe obesity and ID. Use of the NHFS was approved by the institutional review board of Okayama University Hospital, and written informed consent was obtained from the patient's parents. The dental treatment was planned for a 40-year-old male patient (height: 170 cm
body weight : 92.1 kg
body mass index : 31.8) with ID. He had experienced several oxygen desaturation episodes during previous dental sedations because of difficulties encountered during airway management. At this time, the NHFS (Optiflow™) was used for airway management during IVS. Fifty-minutes after the oral administration of 25 mg of midazolam, propofol was continuously infused at a dose of 1.0 μg/ml of the target effect site concentration. The sedation level was maintained at a bispectral index value of 50-70 by adjusting the target concentration of propofol. Initially, 40% oxygen was administered at a rate of 20 l/min via the NHFS. The flow volume was gradually increased up to 50 l/min, and high-flow oxygen was supplied throughout the dental treatment. Neither airway obstruction nor oxygen desaturation was observed during the dental treatment, resulting in no complications such as airway injury. This case suggests that NHFS enabled easy airway management during IVS for dental treatment in an obese patient.

The inhibitory effect of locally injected dexmedetomidine on carrageenan-induced nociception in rats Reviewed

Yuka Honda, Hitoshi Higuchi, Yoshikazu Matsuoka, Akiko Yabuki-Kawase, Minako Ishii-Maruhama, Yumiko Tomoyasu, Shigeru Maeda, Hiroshi Morimatsu, Takuya Miyawaki

European Journal of Pharmacology 764 215 - 219 2015.10

Effect of dexmedetomidine injected into the oral mucosa in combination with lidocaine on local anesthetic potency in humans: a crossover double-blind study. Reviewed International journal

Ayaka Yamane, Hitoshi Higuchi, Yumiko Tomoyasu, Minako Ishii-Maruhama, Shigeru Maeda, Takuya Miyawaki

Journal of oral and maxillofacial surgery 73 ( 4 ) 616 - 621 2015.4

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

PURPOSE: Recently, attention has been paid to dexmedetomidine, a selective α-2 adrenoceptor agonist, as a possible additive for local anesthesia. However, the effect of locally injected dexmedetomidine on the anesthetic action in humans has not fully been clarified. Thus, the purpose of the present study was to evaluate the effect of dexmedetomidine injected into the oral mucosa in combination with lidocaine on local anesthetic potency in humans. MATERIALS AND METHODS: Twenty healthy volunteers were included in the present crossover double-blinded study. Lidocaine solution or lidocaine plus dexmedetomidine solution was submucosally injected into the alveolar mucosa in a crossover and double-blinded manner. The local anesthetic effect of the solutions was evaluated by measuring the current perception threshold (CPT) in the oral mucosa for 120 minutes after injection. Furthermore, the sedation level, blood pressure, and heart rate of the volunteers were evaluated. For statistical analysis, the Wilcoxon signed rank test and 2-way repeated measures analysis of variation were used. RESULTS: The CPT was increased with the 2 solutions and peaked 10 minutes after injection. CPT values 10 and 20 minutes after injection of lidocaine plus dexmedetomidine solution were considerably higher than those with lidocaine solution. The duration of an important increase in the CPT after injection with lidocaine plus dexmedetomidine solution was longer than that with lidocaine. Furthermore, the area under the time curve of CPT was considerably higher with lidocaine plus dexmedetomidine solution than with lidocaine solution. No volunteer showed a change in sedation level, blood pressure, or heart rate after injection with either test solution throughout the experiment. CONCLUSION: The present study showed that a combination of dexmedetomidine plus lidocaine considerably enhances the local anesthetic potency of lidocaine without any major influences on the cardiovascular system when locally injected into the oral mucosa.

DOI： 10.1016/j.joms.2014.09.029

Independent factors affecting recovery time after sedation in patients with intellectual disabilities. Reviewed International journal

Shigeru Maeda, Yumiko Tomayasu, Hitoshi Higuchi, Minako Ishii-Maruhama, Ayaka Yamane, Akiko Yabuki, Yuka Honda, Masahiko Egusa, Takuya Miyawaki

The open dentistry journal 31 146 - 149 2015.3

Language：English Publishing type：Research paper (scientific journal)

Purpose : The purpose of this study was to identify independent factors associated with prolonged recovery time after intravenous sedation for dental treatment in patients with intellectual disabilities. Methods : This study was designed as a prospective cohort study. Participants were patients with intellectual disabilities, for whom sedation for dental treatment was planned in Okayama University Hospital. The outcome variable was recovery time. The predictor variables were patient background, antiepileptic and psychotropic drugs, and anesthesia-related variables. Factors affecting the outcome were examined with multiple regression analysis. Results : We enrolled 260 cases in this study. Oral midazolam was a strong independent determinant in prolonged recovery time. Teeth extraction, short treatment time and lower body mass index were significant independent predictors of prolonged recovery time. Conclusion : Oral midazolam is a clear independent determinant of prolonged recovery time after sedation, while psychotropic drugs and antiepileptic drugs were not independent determinants in this study.

DOI： 10.2174/1874210601509010146

Independent predictors of delay in emergence from general anesthesia Reviewed

Shigeru Maeda, Yumiko Tomoyasu, Hitoshi Higuchi, Minako Ishii-Maruhama, Masahiko Egusa, Takuya Miyawaki

Anesthesia Progress 62 ( 1 ) 8 - 13 2015.3

Language：English Publishing type：Research paper (scientific journal)

Some patients with intellectual disabilities spend longer than others in emergence from ambulatory general anesthesia for dental treatment. Although antiepileptic drugs and anesthetics might be involved, an independent predictor for delay of the emergence remains unclear. Thus, a purpose of this study is to identify independent factors affecting the delay of emergence from general anesthesia. This was a retrospective cohort study in dental patients with intellectual disabilities. Patients in need of sedative premedication were removed from participants. The outcome was time until emergence from general anesthesia. Stepwise multivariate regression analysis was used to extract independent factors affecting the outcome. Antiepileptic drugs and anesthetic parameters were included as predictor variables. The study included 102 cases. Clobazam, clonazepam, and phenobarbital were shown to be independent determinants of emergence time. Parameters relating to anesthetics, patients' backgrounds, and dental treatment were not independent factors. Delay in emergence time in ambulatory general anesthesia is likely to be related to the antiepileptic drugs of benzodiazepine or barbiturates in patients with intellectual disability.

DOI： 10.2344/0003-3006-62.1.8