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布比卡因与肾上腺素或右美托咪定在接受卵巢子宫切除术的猫腹腔内给药后的疗效和药代动力学

Efficacy and pharmacokinetics of bupivacaine with epinephrine or dexmedetomidine after intraperitoneal administration in cats undergoing ovariohysterectomy.

作者信息

Benito Javier, Monteiro Beatriz, Beaudry Francis, Steagall Paulo

机构信息

Department of Clinical Sciences (Benito, Steagall), Biomedical Sciences (Monteiro, Beaudry), and Animal Pharmacology Research Group of Quebec (GREPAQ; Groupe de recherche en pharmacologie animale du Québec) (Monteiro, Beaudry, Steagall), Faculty of Veterinary Medicine, Université de Montréal, Saint-Hyacinthe, Quebec J2S 2M2.

出版信息

Can J Vet Res. 2018 Apr;82(2):124-130.

Abstract

The aim of this study was to determine the efficacy and pharmacokinetics of bupivacaine in combination with epinephrine or dexmedetomidine after intraperitoneal administration in cats undergoing ovariohysterectomy. Sixteen healthy adult cats (3.3 ± 0.6 kg) were included in a prospective, randomized, masked clinical trial after obtaining owners' consent. Anesthetic protocol included buprenorphine-propofol-isoflurane. Meloxicam [0.2 mg/kg body weight (BW)] was administered subcutaneously before surgery. Cats were randomly divided into 2 groups to receive 1 of 2 treatments. Intraperitoneal bupivacaine 0.25% (2 mg/kg BW) was administered with epinephrine (BE group; 2 μg/kg BW) or dexmedetomidine (BD group; 1 μg/kg BW) before ovariohysterectomy ( = 8/group). A catheter was placed in the jugular vein for blood sampling. Blood samples were collected for up to 8 h after bupivacaine was administered. Plasma concentrations and pharmacokinetics of bupivacaine were determined using liquid chromatography tandem mass spectrometry (LC-MS/MS) and non-compartmental model, respectively. Pain was evaluated using the UNESP-Botucatu multidimensional composite pain scale (MCPS), the Glasgow composite feline pain scale (GPS), and a dynamic visual analog scale up to 8 h after extubation. Rescue analgesia was provided with buprenorphine if MCPS was ≥ 6. Repeated measures linear models were used for analysis of pain and sedation scores ( < 0.05). Maximum bupivacaine plasma concentrations (Cmax) for BE and BD were 1155 ± 168 ng/mL and 1678 ± 364 ng/mL ( = 0.29) at 67 ± 13 min (Tmax) and 123 ± 59 min ( = 0.17), respectively. Pharmacokinetic parameters and pain scores were not different between treatments ( > 0.05). One cat in the BE group received rescue analgesia ( = 0.30). Intraperitoneal bupivacaine with epinephrine or dexmedetomidine produced concentrations below toxic levels and similar analgesic effects. It is therefore safe to administer these drug combinations in cats undergoing ovariohysterectomy.

摘要

本研究的目的是确定布比卡因与肾上腺素或右美托咪定联合腹腔注射给药后,在接受卵巢子宫切除术的猫中的疗效和药代动力学。在获得猫主人同意后,16只健康成年猫(体重3.3±0.6千克)被纳入一项前瞻性、随机、双盲临床试验。麻醉方案包括丁丙诺啡-丙泊酚-异氟烷。术前皮下注射美洛昔康[0.2毫克/千克体重(BW)]。猫被随机分为2组,接受两种治疗中的一种。在卵巢子宫切除术(每组n = 8)前,腹腔注射0.25%布比卡因(2毫克/千克BW),同时加入肾上腺素(BE组;2微克/千克BW)或右美托咪定(BD组;1微克/千克BW)。在颈静脉放置导管用于采血。布比卡因给药后最多8小时采集血样。分别使用液相色谱串联质谱法(LC-MS/MS)和非房室模型测定布比卡因的血浆浓度和药代动力学。拔管后长达8小时,使用圣保罗大学-博图卡图多维复合疼痛量表(MCPS)、格拉斯哥复合猫疼痛量表(GPS)和动态视觉模拟量表评估疼痛。如果MCPS≥6,则给予丁丙诺啡进行解救镇痛。采用重复测量线性模型分析疼痛和镇静评分(P < 0.05)。BE组和BD组布比卡因的最大血浆浓度(Cmax)分别在67±13分钟(Tmax)时为1155±168纳克/毫升和123±59分钟时为1678±364纳克/毫升(P = 0.29)。两种治疗之间的药代动力学参数和疼痛评分无差异(P > 0.05)。BE组有1只猫接受了解救镇痛(P = 0.30)。腹腔注射布比卡因联合肾上腺素或右美托咪定产生的浓度低于中毒水平,且镇痛效果相似。因此,在接受卵巢子宫切除术的猫中给予这些药物组合是安全的。

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