首页> 外文期刊>Journal of Pain Research >Continuous wound infusion with chloroprocaine in a pig model of surgical lesion: drug absorption and effects on inflammatory response
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Continuous wound infusion with chloroprocaine in a pig model of surgical lesion: drug absorption and effects on inflammatory response

机译:猪创面模型中连续注射氯普鲁卡因的伤口:药物吸收及其对炎症反应的影响

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Continuous wound infusion (CWI) may protect from inflammation, hyperalgesia and persistent pain. Current local anesthetics display suboptimal pharmacokinetic profile during CWI; chloroprocaine (CP) has ideal characteristics, but has never been tested for CWI. We performed an animal study to investigate the pharmacokinetic profile and anti-inflammatory effect of CP during CWI. A total of 14 piglets received an infusion catheter after pararectal laparotomy and were randomly allocated to one of three groups: 5?mL/h infusion of saline (group A), CP 1.5% (group B) and CP 0.5% (group C). Blood sampling was performed to assess absorption and systemic inflammation at 0, 3, 6, 12, 24, 48, 72, 96, 102 and 108?hours. The wound and contralateral healthy abdominal wall were sampled for histological analyses. Absorption of CP from the site of infusion, evaluated as the plasmatic concentrations of CP and its metabolite, 4-amino-2-chlorobenzoic acid (CABA), showed a peak during the first 6?hours, but both CP and its metabolite rapidly disappeared after stopping CP infusion. Local inflammation was reduced in groups B and C (CP-treated p < 0.001), in a CP dose-dependent fashion. While CP inhibited in a dose-dependent manner pig mononuclear cells (MNCs) in vitro proliferation to a polyclonal activator, no effect on systemic cytokines’ concentrations or on ex vivo monocytes’ responsiveness was observed, suggesting the lack of systemic effects, in line with the very short half-life of CP in plasma. CP showed a very good profile for use in CWI, with dose-dependent local anti-inflammatory effects, limited absorption and rapid clearance from the bloodstream upon discontinuation. No cytotoxicity or side effects were observed. CP, therefore, may represent an optimal choice for clinical CWI, adaptable to each patient’s need, and protective on wound inflammatory response (and hyperalgesia) after surgery.
机译:连续伤口输注(CWI)可以防止发炎,痛觉过敏和持续性疼痛。当前的局部麻醉药在CWI期间显示出次佳的药代动力学特征。氯普鲁卡因(CP)具有理想的特性,但从未经过CWI测试。我们进行了一项动物研究,以研究CWI期间CP的药代动力学特征和抗炎作用。共有14头小猪在直肠旁剖腹手术后接受了输液导管,并随机分配为以下三组之一:A组输注5mL / h盐水(A组),CP 1.5%(B组)和CP 0.5%(C组) 。在0、3、6、12、24、48、72、96、102和108?小时进行采血以评估吸收和全身炎症。对伤口和对侧健康腹壁取样进行组织学分析。从血浆中CP及其代谢物4-氨基-2-氯苯甲酸(CABA)的血浆浓度评估CP从输注部位的吸收,在最初的6小时内出现一个峰值,但CP及其代谢物迅速消失停止CP输注后。 B和C组以CP剂量依赖性方式减少了局部炎症(经CP处理的p <0.001)。尽管CP以剂量依赖性方式抑制猪单核细胞(MNC)在体外向多克隆激活剂的增殖,但未观察到对全身细胞因子浓度或离体单核细胞反应性的影响,表明缺乏全身作用,这与CP在血浆中的半衰期非常短。 CP在CWI中显示出非常好的特性,具有剂量依赖性的局部抗炎作用,吸收受限以及停药后迅速从血流中清除。没有观察到细胞毒性或副作用。因此,CP可能是临床CWI的最佳选择,它可以适应每个患者的需求,并在手术后对伤口的炎症反应(和痛觉过敏)具有保护作用。

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