The Efficacy and Safety of Dexmedetomidine for Sedation During Surgery Under Epidural or Spinal Anesthesia: A Randomized, Double-Blind, Placebo-Controlled Study

Background: Only a few studies have been reported on the use of dexmedetomidine for sedating surgical patients requiring epidural or spinal anesthesia. We conducted a randomized, double-blind, placebo-controlled, parallel-group study at 12 hospitals in Japan. Methods: Adult patients were randomly allocated to receive an intravenous administration of placebo or dexmedetomidine at 0.067, 0.25, 0.5 or 1.0 μg/kg over 10 min after epidural or spinal anesthesia. All dexmedetomidine groups received dexmedetomidine 0.2–0.7 μg/kg/h to maintain an Observer’s Assessment of Alertness/Sedation Scale (OAA/S) score of ≤ 4; however, propofol was administered to rescue patients who exceeded this score. Surgery was then started 15 min after study drug infusion in patients with OAA/S score of ≤ 4. The primary endpoint was the percentage of patients not requiring rescue propofol to achieve and maintain an OAA/S score of ≤ 4. Results: Of the 120 enrolled and randomized patients, 119 were treated the study: 22 received placebo and 97 received dexmedetomidine (23–25 patients per dose). Significantly more patients did not require propofol in the dexmedetomidine 0.5 and 1.0 μg/kg groups (68.0% and 80.0%, respectively) compared to the placebo group (22.7%) (P = 0.003 and P < 0.001, respectively). Common adverse events (AEs) were protocol-defined respiratory depression, bradycardia and hypotension. There was no significant difference in the incidence of AEs between the dexmedetomidine and the placebo groups. Conclusion: We concluded that loading doses of 0.5 and 1.0 μg/kg dexmedetomidine, followed by an infusion at a rate of 0.2–0.7 μg/kg/h, provide effective and well-tolerated sedation for surgical patients during epidural or spinal anesthesia. Clinical trials.gov identifier: NCT0143895

The Efficacy and Safety of Dexmedetomidine for Procedural Sedation in Patients Receiving Local Anesthesia Outside the Intensive Care Unit: A Prospective, Double-Blind, Randomized Clinical Phase III Trial in Japan

Background: Few studies (in other countries than the US) have reported on the efficacy and safety of dexmedetomidine for sedation of patients undergoing surgical or medical procedures under local anesthesia without intubation outside the intensive care unit. We performed a randomized, double-blind study in Japan. Methods: Adult patients were randomly allocated to receive placebo, dexmedetomidine 0.5 μg/kg (DEX 0.5 group), or dexmedetomidine 1.0 μg/kg (DEX 1.0 group) over 10 min. Then, both dexmedetomidine groups received dexmedetomidine 0.2–0.7 μg/kg/h for maintaining an Observer’s Assessment of Alertness/Sedation Scale (OAA/S) score of ≤ 4; however, propofol was administered to rescue patients whose score exceeded this value. The primary endpoint was the percentage of patients who did not require rescue propofol to achieve and maintain an OAA/S score of ≤ 4. Results: In total, 162 patients were included in the placebo (n = 53), DEX 0.5 (n = 53), and DEX 1.0 (n = 56) groups. Propofol was not required in significantly more patients in the dexmedetomidine 0.5 and 1.0 μg/kg groups (52.8% and 57.1%, respectively) compared with the placebo group (1.9%) (P < 0.001 for both). Common adverse events were protocol-defined hypotension, respiratory depression and bradycardia. The incidence of bradycardia was significantly higher in the DEX 0.5 (26.4%) and DEX 1.0 (30.4%) groups than in the placebo group (9.4%) (P = 0.041 and P = 0.008, respectively). Conclusion: We concluded that a loading dose of 0.5 or 1.0 μg/kg dexmedetomidine followed by infusion at a rate of 0.2–0.7 μg/kg/h provided effective and welltolerated sedation in patients undergoing surgical or medical procedures under local anesthesia without intubation. Clinical trials.gov identifier: NCT0143893

肝硬変患者の肝性腹水・浮腫に対するTolvaptan の治療反応性の検討

京都府立医科大学附属北部医療センター消化器内科京都府立医科大学消化器内科学Department of Molecular Gastroenterology and Hepatology, North Medical Center Kyoto Prefectural University of MedicineDepartment of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of MedicineTolvaptan は肝性腹水の治療に非常に有用な薬剤だが、日常臨床ではしばしば無効例を経験する。本研究ではTolvaptan への反応性について、治療前後の腹水、肝予備能、血液生化学的検査の変化を検討したところ、Tolvaptan への反応性は、腎機能、肝予備能に規定されることがわかった。またTolvaptan 無効例でもアルブミン補充や腹水濾過再静注(CART) を併用することで、治療効果の改善を認めた。本研究は少数例の検討であり、今後症例の集積が必要である

低用量アスピリンによる十二指腸輪状潰瘍の一例

京都府立医科大学附属北部医療センター　消化器内科京都府立医科大学消化器内科学Department of Gastroenterology and Hepatology, North Medical Center, Kyoto Prefectural University of MedicineDepartment of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine症例は74歳男性。主訴は腹痛と嘔吐。造影CTにて十二指腸下行脚の壁肥厚と狭窄を認め、上部消化管内視鏡検査では同部位に輪状潰瘍及び高度狭窄を認めた。冠動脈疾患と脳梗塞の既往から低用量アスピリン(LDA)を内服していたためLDA潰瘍と診断した。薬物治療としてボノプラザンの投与を開始し、十二指腸狭窄に対してバルーン拡張術を施行したところ、輪状潰瘍は治癒し現在も再発を認めていない。(著者抄録

難治性肝膿瘍に対する抗菌薬動注療法

京都府立医科大学附属北部医療センター　消化器内科福知山市民病院　放射線科福知山市民病院　消化器内科京都府立医科大学附属北部医療センター　放射線科京都府立医科大学　消化器内科Department of Gastroenterology and Hepatology, North Medical Center, Kyoto Prefectural University of MedicineDepartment of Radiology, Fukuchiyama City HospitalDepartment of Gastroenterology and Hepatology, Fukuchiyama City HospitalDepartment of Radiology, North Medical Center, Kyoto Prefectural University of MedicineDepartment of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine症例は36歳男性。主訴は発熱。肝右葉に多発する内部蜂巣状の膿瘍を認めた。経静脈的抗菌療法により炎症は沈静せず膿瘍は増大した。蜂窩織炎成分主体の病変性状によりドレナージ療法は困難と考え、大腿動脈経由に設置した肝動脈リザーバーを用いて抗菌薬動注療法を開始した。17日目に膿瘍の著明な縮小と炎症反応の鎮静化、28日目に膿瘍は消失した。本例のように従来治療が困難な肝膿瘍に対しては、抗菌薬の肝動注療法が有効である可能性があり、治療法の一つとして考慮する価値がある

大腸Cold Snare Polypectomyにおける手技の工夫とその切除検体の臨床病理学的検討

京都府立医科大学附属北部医療センター　消化器内科京都府立医科大学附属北部医療センター　病理診断科市立福知山市民病院消化器内科京都府立医科大学消化器内科学Department of Gastroentarology and Hepatology, North Medical Center, Kyoto Prefectural University of MedicineDepartment of Pathology, North Medical Center, Kyoto Prefectural University of MedicineDepartment of Gastroentarology and Hepatology, Fukuchiyama City HospitalDepartment of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine Graduate School of Medical Science近年、Cold Snare Polypectomy(CSP) は、その簡便性、安全性から急速に普及しており、当院でも2014年よりCSPを導入している。CSP導入当初の臨床病理学的解析では、病変の完全一括切除率は67％であった。一方、本検討では、3本編細径スネアの導入を含めた手技の工夫により完全一括切除率は94％まで向上を認めた。本研究は少数例の検討であり、今後前向き試験による検討が必要である

アニサキス症による好酸球性肉芽腫を合併した早期胃癌の一例

京都府立医科大学附属北部医療センター　消化器内科京都府立医科大学　消化器内科京都府立医科大学附属北部医療センター　外科Department of Gastroenterology, North Medical Center,Kyoto Prefectural University of MedicineMolecular Gastro enterology and Hepatology, Kyoto Prefectural University of MedicineDepartment of Surgery, North Medical Center,Kyoto Prefectural University of Medicine症例は80代、男性。市民検診での胃透視で前庭部に異常所見を指摘され、精査加療目的に当院受診となった。上部消化管内視鏡検査では胃幽門部に30mm大の3型腫瘍を認めた。生検結果はadenocarcinoma tub2-porであった。胸腹部造影CT検査では所属リンパ節腫大・遠隔転移は認めず、術前診断:cT2N0M0 cStage Iとして手術加療を行った。最終病理診断はadenocarcinoma(por1>tub2>tub1)pT1b(SM2 0.7mm)Ly0V1aN0であり、腫瘍直下の筋層内に2mmの壊死を伴う肉芽腫を認めた。肉芽腫内には好酸球浸潤を認め、遺伝子解析の結果Anisakis simplexが検出された。その後術後経過良好で、現在再発なく、当院外科外来で経過観察されている。(著者抄録

Role and Potential Mechanism of Heme Oxygenase-1 in Intestinal Ischemia-Reperfusion Injury

Intestinal ischemia-reperfusion (IR) injury is a complex, multifactorial, and pathophysiological condition with high morbidity and mortality, leading to serious difficulties in treatment, especially in humans. Heme oxygenase (HO) is the rate-limiting enzyme involved in heme catabolism. HO-1 (an inducible form) confers cytoprotection by inhibiting inflammation and oxidation. Furthermore, nuclear factor-erythroid 2-related factor 2 (Nrf2) positively regulates HO-1 transcription, whereas BTB and CNC homolog 1 (Bach1) competes with Nrf2 and represses its transcription. We investigated the role and potential mechanism of action of HO-1 in intestinal IR injury. Intestinal ischemia was induced for 45 min followed by 4 h of reperfusion in wild-type, Bach1-deficient, and Nrf2-deficient mice, and a carbon monoxide (CO)-releasing molecule (CORM)-3 was administered. An increase in inflammatory marker levels, nuclear factor-κB (NF-κB) activation, and morphological impairments were observed in the IR-induced intestines of wild-type mice. These inflammatory changes were significantly attenuated in Bach1-deficient mice or those treated with CORM-3, and significantly exacerbated in Nrf2-deficient mice. Treatment with an HO-1 inhibitor reversed this attenuation in IR-induced Bach1-deficient mice. Bach1 deficiency and treatment with CORM-3 resulted in the downregulation of NF-κB activation and suppression of adhesion molecules. Together, Bach1, Nrf2, and CO are valuable therapeutic targets for intestinal IR injury