Faculty Profiles - HIGUCHI Hitoshi

Papers - HIGUCHI Hitoshi

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The clinical advantage of nasal high-flow in respiratory management during procedural sedation: A scoping review on the application of nasal high-flow during dental procedures with sedation. Reviewed International journal

Shinji Kurata, Takuro Sanuki, Hitoshi Higuchi, Takuya Miyawaki, Seiji Watanabe, Shigeru Maeda, Shuntaro Sato, Max Pinkham, Stanislav Tatkov, Takao Ayuse

The Japanese dental science review 58 179 - 182 2022.11

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

Structured summary: Rationale: Nasal high-flow (NHF), a new method for respiratory management during procedural sedation, has greater advantages than conventional nasal therapy with oxygen. However, its clinical relevance for patients undergoing oral maxillofacial surgery and/or dental treatment remains uncertain and controversial, due to a paucity of studies. This scoping review compared and evaluated NHF and conventional nasal therapy with oxygen in patients undergoing oral maxillofacial surgery and/or dental treatment. Materials and methods: A literature search of two public electronic databases was conducted, and English writing randomized controlled trials (RCTs) of nasal high flow during dental procedure with sedation reviewed. The primary and secondary outcomes of interest were the incidence of hypoxemia and hypercapnia during sedation and the need for intervention to relieve upper airway obstruction, respectively. Results: The search strategy yielded 7 studies, of which three RCTs met our eligibility criteria, with a total of 78 patients. Compared with conventional nasal therapy with oxygen, NHF significantly reduced the incidence of hypoxemia and hypercapnia during procedural sedation. Conclusion: NHF can maintain oxygenation and possibly prevent hypercapnia in patients undergoing dental treatment. Additional RCTs are needed to clarify and confirm these findings.

DOI： 10.1016/j.jdsr.2022.05.003

Capsaicin May Improve Swallowing Impairment in Patients with Amyotrophic Lateral Sclerosis: A Randomized Controlled Trial. Reviewed

Tomoko Higashi, Naomichi Murata, Maki Fujimoto, Saki Miyake, Masahiko Egusa, Hitoshi Higuchi, Shigeru Maeda, Takuya Miyawaki

Acta medica Okayama 76 ( 2 ) 179 - 186 2022.4

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

Patients with neurodegenerative diseases are at an increased risk of dysphagia and aspiration pneumonia. In this study, we examined whether ingestion of capsaicin prior to swallowing changes the temporal dynamics of swallowing in such patients. In a crossover, randomized controlled trial, 29 patients with neurodegenerative diseases were given a soluble wafer containing 1.5 μg capsaicin or an identical placebo 20 min prior to testing. For evaluation with video fluoroscopy (VF), patients consumed a barium-containing liquid plus thickening material. The durations of the latency, elevating and recovery periods of the hyoid were assessed from VF. Overall, no significant differences were observed in the duration of each period between capsaicin and placebo treatments. However, reductions in the latency and elevating periods were positively correlated with baseline durations. In subgroup analyses, that correlation was observed in patents with amyotrophic lateral sclerosis (ALS) but not in patients with Parkinson's disease. The consumption of wafer paper containing capsaicin before the intake of food may be effective in patients with dysphagia related with certain neurodegenerative diseases, particularly ALS patients. Further studies will be needed to validate this finding.

DOI： 10.18926/AMO/63412

Reply Invited International journal

Hitoshi Higuchi, Kumiko Takaya-Ishida, Saki Miyake, Maki Fujimoto, Yukiko Nishioka, Shigeru Maeda, Takuya Miyawaki

Journal of Oral and Maxillofacial Surgery 79 ( 11 ) 2181 - 2182 2021.11

知的障害者の安全な麻酔管理を目指して Invited Reviewed

樋口仁

日本歯科麻酔学会雑誌 49 ( 4 ) 158 - 157 2021.10

Patient satisfaction with deep versus light/moderate sedation for non-surgical procedures Reviewed International journal

Hiroshi Hoshijima, Hitoshi Higuchi, Aiji Sato (Boku), Makiko Shibuya, Yoshinari Morimoto, Toshiaki Fujisawa, Kentaro Mizuta

Medicine 100 ( 36 ) e27176 - e27176 2021.9

Language：English Publishing type：Research paper (scientific journal) Publisher：Ovid Technologies (Wolters Kluwer Health)

BACKGROUND: Deep sedation relieves a patient's anxiety and stress during the procedure by inducing patient unconsciousness. However, it remains unclear whether deep sedation actually improves patient satisfaction with the procedure. Therefore, we performed a systematic review and meta-analysis to compare the satisfaction of patients undergoing deep sedation with that of those undergoing light/moderate sedation during non-surgical procedures. METHODS: A comprehensive literature search was performed using electronic databases (search until September 2020). The primary outcome was whether patient satisfaction was higher after deep sedation or light/moderate sedation. The secondary outcome was the relative safety of deep sedation compared with light/moderate sedation in terms of oxygen saturation, systolic blood pressure, and heart rate. The tertiary outcomes were the relative procedure and recovery times for deep versus light/moderate sedation.Data from each of the trials were combined, and calculations were made using DerSimonian and Laird random effects models. The pooled effect estimates for patient satisfaction were evaluated using relative risk (RR) with the 95% confidence interval (CI). The pooled effect estimates for continuous data are expressed as weighted mean difference with the 95% CI. We assessed heterogeneity with the Cochrane Q statistic and the I2 statistic. The risk of bias assessment and Grading of Recommendations Assessment, Development and Evaluation approach were used as the quality assessment method. RESULTS: After removing unrelated studies and applying the exclusion criterion, 5 articles satisfied the inclusion criteria. Patient satisfaction was significantly higher in those who received deep sedation compared with light/moderate sedation (relative risk = 1.12; 95% CI, 1.04-1.20; P = .003; Cochrane Q = 25.0; I2 = 76%).There was no significant difference in oxygen saturation, systolic blood pressure, heart rate, and procedure times according to whether the procedures were performed under deep or light/moderate sedation. However, the recovery time was significantly prolonged in patients under deep sedation. CONCLUSIONS: Our meta-analysis suggests that deep sedation resulted in improved patient satisfaction compared with light/moderate sedation. Deep sedation is recommended for patients undergoing procedures because it improves patient satisfaction. However, respiration and circulation should be carefully monitored both intra-operatively and postoperatively.

DOI： 10.1097/md.0000000000027176

Comparison of Oxygen Saturation Between Nasal High-Flow Oxygen and Conventional Nasal Cannula in Obese Patients Undergoing Dental Procedures With Deep Sedation: A Randomized Crossover Trial Reviewed International journal

Hitoshi Higuchi, Kumiko Takaya-Ishida, Saki Miyake, Maki Fujimoto, Yukiko Nishioka, Shigeru Maeda, Takuya Miyawaki

Journal of Oral and Maxillofacial Surgery 79 ( 9 ) 1842 - 1850 2021.9

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

PURPOSE: In anesthetic management, it is widely accepted that obese patients are more likely to suffer airway obstructions and reductions in arterial oxygen saturation (SpO2). Therefore, it is important to take special measures to prevent oxygen desaturation during the deep sedation of obese patients. This clinical study examined whether the use of nasal high-flow systems (NHFS) keep higher SpO2 and reduced hypoxemia than conventional nasal cannula during the deep sedation of obese patients with intellectual disabilities for dental treatment. MATERIALS AND METHODS: Eighteen obese patients (body mass index: >25) with intellectual disabilities who underwent dental sedation were enrolled. In each case, sedation was induced using propofol and maintained at a bispectral index of 50 to 70. The subjects were randomly assigned to the control oxygen administration (5 L/min via a nasal cannula) or NHFS (40% O2, 40 L/min, 37 °C) arm in alternate shifts as a crossover trial. The primary endpoint was the minimum SpO2 value, and the incidence of hypoxemia during dental treatment was also evaluated. RESULTS: The mean minimum SpO2 value was significantly higher in the NHFS arm than in the control arm (95.8 ± 2.1 % vs 93.6 ± 4.1 %, P = 0.0052, 95% confidence interval: 0.608-3.947). Hypoxemic episodes (SpO2: ≤94%) occurred 3 cases (16.7%) in the NHFS arm and 11 cases (61.1%) in the control arm (P = 0.0076, odds ratio: 0.127, 95% confidence interval 0.0324 - 0.630). CONCLUSION: NHFS resulted in higher minimum SpO2 and reduced hypoxemia than nasal cannula in obese patients during deep sedation for dental treatment.

DOI： 10.1016/j.joms.2021.04.004

Evaluation of the Safety and Pharmacokinetics of Articaine Hydrochloride and Adrenaline Bitartrate (OKAD01) for Local Anesthesia in Dentistry : A Phase Ⅰ, Single Center, Non-blinded Study Reviewed

HIGUCHI Hitoshi, HONDA-WAKASUGI Yuka, YABUKI-KAWASE Akiko, MAEDA Shigeru, MIYAWAKI Takuya

Journal of Japanese Dental Society of Anesthesiology 49 ( 3 ) 81 - 96 2021.7

Authorship：Lead author,　Corresponding author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The Japanese Dental Society of Anesthesiology

<p> Purpose : Articaine hydrochloride is commonly used as a local anesthetic for dentistry in many countries. However, this compound has not been approved for use in Japan. To support the approval of articaine hydrochloride and adrenaline bitartrate (OKAD01) in Japan, we performed a phase Ⅰ clinical trial to clarify the pharmacokinetics and safety of injecting OKAD01 into the oral mucosae of healthy Japanese adults.</p><p> Methods : The subjects were healthy Japanese male adults. One (1.7 ml) or 3 cartridges (5.1 ml) of OKAD01 were injected into the oral mucosae of 6 subjects each. The blood concentration of articaine was measured before the injection and at 15 min, 30 min, 60 min, 2 h, 4 h, 12 h, and 24 h after the injection. Clinical laboratory tests and vital sign measurements were also performed, and adverse events were evaluated during this clinical trial.</p><p> Results : In the 1-cartridge trial, the maximum blood concentration (Cmax) and the time taken to reach it (Tmax) were 374.35±97.65 (252.7-514.5) ng/ml and 0.25±0.00 (0.25-0.25) h, respectively (mean±SD (minimum-maximum)). In the 3-cartridge trial, the Cmax and Tmax were 694.00±175.23 (517.9-970.4) ng/ml and 0.42±0.13 (0.25-0.5) h, respectively. Regarding adverse events, we encountered 1 case of headache in the 1-cartridge trial ; however, this event was not thought to be associated with the OKAD01 injection.</p><p> Conclusion : Injecting OKAD01 into the oral mucosae of healthy Japanese adults resulted in a Cmax of <5.0 μg/ml and did not cause any adverse events. This study demonstrated the safety and tolerability of OKAD01 in the Japanese population.</p>

DOI： 10.24569/jjdsa.49.3_81

A Case of Delayed Emergence from General Anesthesia with Propofol in an Outpatient Receiving Multi-drug Therapy for Epilepsy Reviewed

HONDA-WAKASUGI Yuka, YABUKI-KAWASE Akiko, UJITA Hitomi, HAMAOKA Midori, HIGUCHI Hitoshi, MAEDA Shigeru, MIYAWAKI Takuya

Journal of Japanese Dental Society of Anesthesiology 49 ( 1 ) 1571 - 3 2021.1

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

<p> Patients with intellectual disabilities frequently have concomitant epilepsy requiring medication with multiple antiepileptic drugs. Some previous studies have reported a drug interaction between propofol and antiepileptics. We report an outpatient with a delayed emergence from a general anesthesia with propofol that was attributed to multi-drug therapy for epilepsy.</p><p> The patient was a 44-year-old man who was scheduled to undergo dental treatment requiring two sessions of ambulatory anesthesia using propofol. His preoperative tests were normal, including a routine blood examination, liver and kidney function, ECG and chest radiograph. He was receiving multiple antiepileptic drugs for the treatment of epilepsy. </p><p> Anesthesia was induced using propofol, remifentanil, and rocuronium bromide. After the discontinuation of propofol administration, spontaneous eye opening and a response to verbal commands were both delayed, occurring about 1 hour after the first session of general anesthesia and about 1.5 hours after the second session.</p><p> The patient was not obese, and his perioperative liver and renal functions were normal. Hypothermia and central nervous system (CNS) abnormalities caused by sequela were both ruled out. He had been receiving multiple antiepileptic drugs, so synergistic effects at propofol's site of action in the CNS were suspected as the main cause of the delayed emergence. Furthermore, hypovolemia could have resulted in an elevated blood level of propofol and its delayed metabolism/excretion, delaying the emergence from sedation.</p><p> We could not identify a clear cause because we did not measure the blood concentrations of the antiepileptics or propofol in the patient. In the presently reported patient, a drug interaction between propofol and antiepileptics was thought to be a possible cause of the delayed emergence from sedation.</p><p></p>

DOI： 10.24569/jjdsa.49.1_1

Pulmonary Aspiration During Induction of General Anesthesia Reviewed International journal

Reina Hayashi, Shigeru Maeda, Taninishi Hideki, Hitoshi Higuchi, Takuya Miyawaki

Anesthesia Progress 67 ( 4 ) 214 - 218 2020.12

Language：English Publishing type：Research paper (scientific journal) Publisher：American Dental Society of Anesthesiology (ADSA)

Perioperative pulmonary aspiration of gastric contents can induce complications of varying severity, including aspiration pneumonitis or pneumonia, which may be lethal. A 34-year-old man with no significant medical history presented to Okayama University Hospital for extraction of the third molars and incisive canal cystectomy under general anesthesia. He experienced pulmonary aspiration of clear stomach fluid during mask ventilation after induction. After aspiration occurred, the patient was immediately intubated, and suctioning was performed through the endotracheal tube (ETT). An anteroposterior (AP) chest radiograph was obtained that demonstrated atelectasis in the left lower lobe, in addition to increased peak airway pressures being noted, although SpO2 remained at 96% to 99% at an FiO2 of 1.0. The decision was made to proceed, and the scheduled procedures were completed in approximately 2 hours. A repeat AP chest radiograph obtained at the end of the operation revealed improvement of the atelectasis, and no residual atelectasis was observed on the next day. Although the patient reported following standard preoperative fasting instructions (no fluids for 2 hours preoperatively), more than 50 mL of clear fluid remained in his stomach. Because vomiting can occur despite following NPO guidelines, the need for continued vigilance by anesthesia providers and proper timely management is reinforced.

DOI： 10.2344/anpr-67-02-03

Dexmedetomidine inhibits LPS-induced inflammatory responses through peroxisome proliferator-activated receptor gamma (PPARγ) activation following binding to α2 adrenoceptors Reviewed

Maki Fujimoto, Hitoshi Higuchi, Yuka Honda-Wakasugi, Saki Miyake, Yukiko Nishioka, Akiko Yabuki-Kawase, Shigeru Maeda, Takuya Miyawaki

European Journal of Pharmacology 892 173733 2020.11

Metabolic alterations caused by the mutation and overexpression of the Tmem135 gene Reviewed

Wei-Hua Lee, Vijesh J Bhute, Hitoshi Higuchi, Sakae Ikeda, Sean P Palecek, Akihiro Ikeda

Experimental Biology and Medicine 245 ( 17 ) 1571 - 1583 2020.11

知的障害を伴ったGlenn術後患者の静脈内鎮静法の経験 Reviewed

宇治田仁美, 若杉優花, 中納麻衣, 西岡由紀子, 樋口仁, 前田茂, 宮脇卓也

日本歯科麻酔学会雑誌 48 ( 4 ) 138 - 140 2020.10

Language：Japanese Publisher：(一社)日本歯科麻酔学会

症例は9歳6ヵ月男児で、乳歯4歯の晩期残存を認めたが、複雑心奇形の合併、最重度の知的障害および身体障害により通法下での抜歯が困難であるため、麻酔管理下での抜歯を目的に当科を紹介され受診した。浸潤麻酔は1/8万アドレナリン含有2%リドカインを生理食塩液で2倍に希釈したものを総量1.2mL投与した。術中に体動が再度出現した際はケタミンを5mgずつ静脈内投与した。スケーリング終了後、酸素投与量を2L/minに減量し、聴診器にて肺音が正常であることを確認した。その25分後、開眼、体動によって覚醒を確認し、心拍数は126回/分、SpO2は87%と術前と変わりないことを確認した後に酸素投与量を1L/minとして退室した。鎮痛指示はカロナール細粒150mgを処方したが、痛がる様子がなかったため内服させなかった。その後も経過良好のため翌日退院となった。

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Assessing the Effectiveness of Combined Analgesics for Bilateral Ramus Osteotomies Reviewed

Shigeru Maeda, Hitoshi Higuchi, Maki Fujimoto, Saki Miyake, Yuka Honda-Wakasugi, Takuya Miyawaki

Anesthesia Progress 67 ( 3 ) 140 - 145 2020.9

Assessing the Effectiveness of Combined Analgesics for Bilateral Ramus Osteotomies

Shigeru Maeda, Hitoshi Higuchi, Maki Fujimoto, Saki Miyake, Yuka Honda-Wakasugi, Takuya Miyawaki

Anesthesia progress 67 ( 3 ) 140 - 145 2020.9

Language：English Publishing type：Research paper (scientific journal) Publisher：NLM (Medline)

Pain management is important for alleviating patients' suffering and early recovery. Although analgesic combinations are known to be effective, a comparison of the effectiveness of different combinations has never been performed specifically for ramus osteotomy procedures. Therefore, the purpose of this observational retrospective cohort study was to identify an effective combination for pain management throughout the intraoperative and immediate postoperative period for patients undergoing bilateral ramus osteotomy procedures. Inclusion criteria consisted of patients who had undergone bilateral mandibular ramus osteotomies over a 2-year period. The analyzed predictor variables included patient gender, age, body weight, operation, anesthetic method, duration of operation, intraoperative use of fentanyl, nonsteroidal anti-inflammatory drugs (NSAIDs), and intravenous acetaminophen administered in the operating room at the end of the surgery. The outcome variable was the necessity for additional rescue analgesics (yes/no) in the recovery room. Bivariate statistics and multivariate analysis were computed with a p-value of &lt
0.05. The study sample was comprised of 78 patients requiring bilateral mandibular ramus osteotomies. From the multivariate analysis, the combination of NSAIDs-acetaminophen-fentanyl was an independent factor for no additional rescue analgesics during the first 1 hour after bilateral ramus osteotomies, indicating that the combination is significantly effective for bilateral ramus osteotomies compared with the other combinations. Considering that this study consisted of a small sample size, the results of this study suggest that some of the combinations, particularly NSAIDs-acetaminophen-fentanyl, are more effective than NSAIDs alone for postoperative pain control immediately following bilateral ramus osteotomy procedures.

DOI： 10.2344/anpr-67-01-05

大腿骨低形成・特異顔貌症候群患者の全身麻酔経験 Reviewed

松田怜奈, 濱岡緑, 三宅沙紀, 若杉優花, 樋口仁, 前田茂, 宮脇卓也

日本歯科麻酔学会雑誌 48 ( 2 ) 57 - 59 2020.4

Language：Japanese Publisher：(一社)日本歯科麻酔学会

17歳女性。開口障害があり、開口量は10mm程度であった。夜間睡眠時に一時的な呼吸停止を認めた既往があり、睡眠時無呼吸の疑いを指摘されていた。開口障害に対して開口量改善および睡眠時無呼吸の改善を目的に下顎骨延長術の実施が検討され、それに先立ち今回、全身麻酔下での筋突起切除術が予定された。麻酔管理上の問題として、骨格異常と小顎による気道確保困難および気管挿管困難が危惧されたが、自発呼吸が残る程度に適度な鎮静を図ったうえで、気管支ファイバースコープを用いて意識下挿管することにより安全な気道管理が行えた。

Multi-drug therapy for epilepsy influenced bispectral index after a bolus propofol administration without affecting propofol's pharmacokinetics: a prospective cohort study. Reviewed International journal

Matsuri Kodama, Hitoshi Higuchi, Minako Ishii-Maruhama, Mai Nakano, Yuka Honda-Wakasugi, Shigeru Maeda, Takuya Miyawaki

Scientific reports 10 ( 1 ) 1578 - 1578 2020.1

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

Some previous studies have indicated that valproate (VPA) might change the pharmacokinetics and enhance the effects of propofol. We evaluated whether clinical VPA therapy affected the propofol blood level, the protein-unbound free propofol level, and/or the anesthetic effects of propofol in the clinical setting. The subjects were divided into the control group (not medicated with antiepileptics), the mono-VPA group (medicated with VPA alone), and the poly-VPA group (medicated with VPA, other antiepileptics, and/or psychoactive drugs). General anesthesia was induced via the administration of a single bolus of propofol and a remifentanil infusion, and when the bispectral index (BIS) exceeded 60 sevoflurane was started. There were no significant differences in the total blood propofol level at 5, 10, 15, and 20 min or the protein-unbound free propofol level at 5 min after the intravenous administration of propofol between the 3 groups. However, the minimum BIS was significantly lower and the time until the BIS exceeded 60 was significantly longer in the poly-VPA group. In the multivariate regression analysis, belonging to the poly-VPA group was found to be independently associated with the minimum BIS value and the time until the BIS exceeded 60. Clinical VPA therapy did not influence the pharmacokinetics of propofol. However, multi-drug therapy involving VPA might enhance the anesthetic effects of propofol.

DOI： 10.1038/s41598-020-58460-2

歯科麻酔専門医・認定医における深鎮静の現状認識調査報告 Reviewed

渋谷真希子, 佐藤會士[朴], 樋口仁, 星島宏, 森本佳成, 藤澤俊明, 日本歯科麻酔学会歯科麻酔医のための深鎮静ガイドライン策定小部会

日本歯科麻酔学会雑誌 48 ( 1 ) 22 - 29 2020.1

Language：Japanese Publisher：(一社)日本歯科麻酔学会

日本歯科麻酔学会歯科麻酔専門医全員292名と歯科麻酔認定医資格のみ有する歯科麻酔医から無作為に抽出した308名を対象として、2018年8月に電子メールにより深鎮静に対する現状意識に関するアンケート調査を実施した。回答率は40.2%であり、歯科麻酔専門医が154名、歯科麻酔認定医資格のみを有する者が87名であった。所属する施設で深鎮静が行われていた割合は71.4%であった。アメリカ麻酔学会(ASA)の呼びかけや刺激に対する反応から見た鎮静深度区分(「ASA鎮静深度区分」)とRamsay's sedation scaleを融合かつ改変して鎮静深度スコア1〜6を作成し、回答者が考える深鎮静の深度範囲を調査した結果、「ASA鎮静深度区分」で中等度鎮静に属するスコア5-aを「最浅」と選択したものが多く(40.7%)、「最深」と考えるスコアはスコア5-cとスコア6がそれぞれ41.9%、36.1%で拮抗するなど、「最浅」「最深」ともにその範囲の選択は多様であった。

歯科麻酔医の深鎮静に関する施設実態調査報告 Reviewed

渋谷真希子, 佐藤會士[朴], 樋口仁, 星島宏, 森本佳成, 藤澤俊明, 日本歯科麻酔学会歯科麻酔医のための深鎮静ガイドライン策定小部会

日本歯科麻酔学会雑誌 47 ( 4 ) 158 - 164 2019.10

Language：Japanese Publisher：(一社)日本歯科麻酔学会

歯科麻酔医が勤務する歯科施設を対象に深鎮静管理に関するアンケート調査を行った。その結果、189施設中109施設(57.7%)から回答が得られた。深鎮静の定義に関しては56.9%の施設で共通した定義がなく、また、定義のある施設でも文書化されているのは10.6%であった。実際に深鎮静を行っている施設は76.1%であった。気道管理に関わる偶発症を経験した施設の割合は、重複を含め、喉頭痙攣が12.0%、誤嚥が24.1%、気管挿管やBag-valve-maskによる対応を要した気道閉塞・呼吸抑制が36.1%であった。今回の検討ではスタッフ間で深鎮静に対する共通した認識があるとは限らないことや、意識下鎮静と比べ偶発症のリスクが高い可能性が示唆された。

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Locally injected ivabradine inhibits carrageenan-induced pain and inflammatory responses via hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Reviewed International journal

Saki Miyake, Hitoshi Higuchi, Yuka Honda-Wakasugi, Maki Fujimoto, Hotaka Kawai, Hitoshi Nagatsuka, Shigeru Maeda, Takuya Miyawaki

PloS one 14 ( 5 ) e0217209 2019.5

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

BACKGROUND: Recently, attention has been focused on the role of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in the mechanism of and as a treatment target for neuropathic and inflammatory pain. Ivabradine, a blocker of HCN channels, was demonstrated to have an effect on neuropathic pain in an animal model. Therefore, in the present study, we evaluated the effect of ivabradine on inflammatory pain, and under the hypothesis that ivabradine can directly influence inflammatory responses, we investigated its effect in in vivo and in vitro studies. METHODS: After approval from our institution, we studied male Sprague-Dawley rats aged 8 weeks. Peripheral inflammation was induced by the subcutaneous injection of carrageenan into the hindpaw of rats. The paw-withdrawal threshold (pain threshold) was evaluated by applying mechanical stimulation to the injected site with von Frey filaments. Ivabradine was subcutaneously injected, combined with carrageenan, and its effect on the pain threshold was evaluated. In addition, we evaluated the effects of ivabradine on the accumulation of leukocytes and TNF-alpha expression in the injected area of rats. Furthermore, we investigated the effects of ivabradine on LPS-stimulated production of TNF-alpha in incubated mouse macrophage-like cells. RESULTS: The addition of ivabradine to carrageenan increased the pain threshold lowered by carrageenan injection. Both lamotrigine and forskolin, activators of HCN channels, significantly reversed the inhibitory effect of ivabradine on the pain threshold. Ivabradine inhibited the carrageenan-induced accumulation of leukocytes and TNF-alpha expression in the injected area. Furthermore, ivabradine significantly inhibited LPS-stimulated production of TNF-alpha in the incubated cells. CONCLUSION: The results of the present study demonstrated that locally injected ivabradine is effective against carrageenan-induced inflammatory pain via HCN channels. Its effect was considered to involve not only an action on peripheral nerves but also an anti-inflammatory effect.

DOI： 10.1371/journal.pone.0217209

Marshall-Smith症候群患児の全身麻酔経験 Reviewed

中納麻衣, 藤本磨希, 三宅沙紀, 谷村博史, 樋口仁, 前田茂, 宮脇卓也

日本歯科麻酔学会雑誌 47 ( 2 ) 47 - 49 2019.4

Language：Japanese Publisher：(一社)日本歯科麻酔学会

症例は10歳男児で、生後1ヵ月時に中顔面の低形成、多関節拘縮、尿道下裂、小下顎症、体幹が細いことなどから染色体検査を受け、Marshall-Smith症候群の診断を受けた。今回、正中過剰埋伏歯に対して抜歯術が予定された。酸素6L/minを吸入させ、プロポフォール20mgを投与し、引き続き10mg/kg/hで持続的に投与した。気道確保の後、セボフルランを3%の濃度で開始し、徐々に人工呼吸に移行した。その後セボフルラン濃度を5%に変更し、McGRATH MACで愛護的に喉頭展開を試みたところ声帯が確認でき、挿管可能と判断した。術中はプロポフォールとフェンタニルで維持した。手術終了後、自発呼吸の回復および十分な覚醒を確認した後、抜管を行った。抜管に際して、骨折を誘発するような体動および興奮は認めなかった。周術期を通して経皮的動脈血酸素飽和度の低下はみられず、術後も経過良好のため翌日退院となった。

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