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达金氏溶液的快速降解和非选择性使其在受污染的肌肉骨骼创伤模型中无法发挥有效作用。

Rapid degradation and non-selectivity of Dakin's solution prevents effectiveness in contaminated musculoskeletal wound models.

作者信息

Mangum Lee C, Franklin Nathan A, Garcia Gerardo R, Akers Kevin S, Wenke Joseph C

机构信息

Extremity Trauma and Regenerative Medicine, United States Army Institute of Surgical Research, Fort Sam Houston, TX, USA.

Extremity Trauma and Regenerative Medicine, United States Army Institute of Surgical Research, Fort Sam Houston, TX, USA; Brooke Army Medical Center, Fort Sam Houston, TX, USA.

出版信息

Injury. 2018 Oct;49(10):1763-1773. doi: 10.1016/j.injury.2018.08.004. Epub 2018 Aug 6.

Abstract

BACKGROUND

Dakin's solution (buffered sodium hypochlorite) has been used as a topical adjunct for the treatment of invasive fungal infections in trauma patients. Prudent use of Dakin's solution (DS) for complex musculoskeletal wound management implies balancing antimicrobial efficacy and human tissue toxicity, but little empirical evidence exists to inform clinical practice. To identify potentially efficacious DS concentrations and application methods, we conducted two animal studies to evaluate the ability of DS to reduce bacterial burden in small and large animal models of contaminated musculoskeletal wounds.

METHODS

An established rat (Rattus norvegicus) contaminated femoral defect model was employed to evaluate the antimicrobial efficacy of DS as a topical adjunctive treatment for Staphylococcus aureus infection. A range of clinically-relevant DS concentrations (0.00025%-0.125%) were tested, both with and without periodic replenishment during treatment. Next, an established goat (Capra hircus) musculoskeletal wound model, consisting of a Pseudomonas aeruginosa contaminated proximal tibia cortical defect, muscle crush, and thermal injury, was utilized to evaluate the antimicrobial efficacy of dilute DS (0.0025% and 0.025%) as a surgical irrigant solution. In situ reactive chlorine concentrations were monitored throughout each treatment using an automated iodometric titration approach.

RESULTS

In a rat wound model, DS treatment did not significantly reduce S. aureus bioburden after 14 days as compared to saline control. Two treatment groups (0.01% single application and 0.025% multiple application) exhibited significantly higher bacterial burden than control. In a goat musculoskeletal wound model, neither 0.0025% nor 0.025% DS significantly altered P. aeruginosa bioburden immediately following treatment or at 48 h post-treatment. Overall, DS applied to exposed soft tissue exhibited rapid degradation, e.g., 0.125% DS degraded 32% after 5 s progressing to 86% degradation after 15 min following single application.

CONCLUSIONS

We did not observe evidence of a therapeutic benefit following Dakin's solution treatment for any tested concentration or application method in two contaminated musculoskeletal wound models. Despite confirmation of robust bactericidal activity in vitro, our findings suggest DS at current clinically-used concentrations does not kill tissue surface-attached bacteria, nor does it necessarily cause host tissue toxicity that exacerbates infection in the setting of complex musculoskeletal injury.

摘要

背景

达金氏溶液(缓冲次氯酸钠)已被用作创伤患者侵袭性真菌感染的局部辅助治疗药物。谨慎使用达金氏溶液(DS)进行复杂的肌肉骨骼伤口处理意味着要平衡抗菌效果和对人体组织的毒性,但几乎没有实证证据可指导临床实践。为了确定可能有效的DS浓度和应用方法,我们进行了两项动物研究,以评估DS在受污染肌肉骨骼伤口的小型和大型动物模型中降低细菌负荷的能力。

方法

采用已建立的大鼠(褐家鼠)污染股骨缺损模型,评估DS作为金黄色葡萄球菌感染局部辅助治疗的抗菌效果。测试了一系列临床相关的DS浓度(0.00025%-0.125%),治疗期间有或没有定期补充。接下来,利用已建立的山羊(山羊属)肌肉骨骼伤口模型,该模型由铜绿假单胞菌污染的胫骨近端皮质缺损、肌肉挤压和热损伤组成,评估稀释的DS(0.0025%和0.025%)作为手术冲洗液的抗菌效果。在每次治疗过程中,使用自动碘量滴定法监测原位活性氯浓度。

结果

在大鼠伤口模型中,与生理盐水对照相比,DS治疗14天后金黄色葡萄球菌生物负荷没有显著降低。两个治疗组(单次应用0.01%和多次应用0.025%)的细菌负荷显著高于对照组。在山羊肌肉骨骼伤口模型中,0.0025%和0.025%的DS在治疗后立即或治疗后48小时均未显著改变铜绿假单胞菌的生物负荷。总体而言,应用于暴露软组织的DS降解迅速,例如,单次应用后,0.125%的DS在5秒后降解32%,15分钟后降解至86%。

结论

在两个受污染的肌肉骨骼伤口模型中,对于任何测试浓度或应用方法,我们都未观察到达金氏溶液治疗有治疗益处的证据。尽管在体外证实了强大的杀菌活性,但我们的研究结果表明,目前临床使用浓度的DS不能杀死附着在组织表面的细菌,也不一定会导致宿主组织毒性,从而在复杂的肌肉骨骼损伤情况下加剧感染。

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