University of California, San Francisco, California.
Ludwig Boltzmann Institute for Experimental and Clinical Traumatology in the AUVA Research Center, Vienna, Austria.
Shock. 2019 Jan;51(1):33-43. doi: 10.1097/SHK.0000000000001209.
As outlined in the "International Guidelines for Management of Sepsis and Septic Shock: 2016," initial fluid resuscitation and administration of antibiotics are key steps in the early management of sepsis and septic shock. However, such clear guidelines do not exist for preclinical sepsis models. To address these shortcomings, the Wiggers-Bernard conference on preclinical sepsis models was held in Vienna in May 2017. The participants reviewed 260 of the most highly cited papers between 2003 and 2012 that used sepsis models. The review demonstrated that over 70% of experiments either did not use or failed to report resuscitation and/or antibiotic treatment. This information served as the basis to create a series of recommendations and considerations for preclinical sepsis models; this Part III report details the recommendations for fluid resuscitation and antibiotic treatment that should be addressed in sepsis models. Similar to human sepsis, fluid resuscitation is recommended in the experimental setting unless part of the study. Iso-osmolar crystalloid solutions are preferred. The administration route and its timing should be adjusted to the specific requirements of the model with preference given to dynamic rather than static hemodynamic monitoring. Predefined endpoints for fluid resuscitation and avoidance of fluid overload should be considered. Preclinical sepsis studies display serious inconsistencies in the use of antimicrobial protocols. To remedy this, antimicrobials are recommended for preclinical studies, with choice and dose adjusted to the specific sepsis model and pathogen (s). Ideally, the administration of antimicrobials should closely mimic clinical practice, taking into account the drug's pharmacokinetic profile, alterations in absorption, distribution and clearance, and host factors such as age, weight, and comorbidities. These recommendations and considerations are proposed as "best practices" for animal models of sepsis that should be implemented.
正如《国际脓毒症和脓毒性休克管理指南：2016》所述，初始液体复苏和抗生素治疗是脓毒症和脓毒性休克早期管理的关键步骤。然而，临床前脓毒症模型并不存在这样明确的指南。为了解决这些不足，2017 年 5 月在维也纳举行了 Wiggers-Bernard 临床前脓毒症模型会议。与会者回顾了 2003 年至 2012 年期间使用脓毒症模型的 260 篇被引用最多的论文。审查表明，超过 70%的实验要么没有进行液体复苏和/或抗生素治疗，要么没有报告。这些信息为制定临床前脓毒症模型的一系列建议和注意事项提供了依据；第三部分报告详细介绍了临床前脓毒症模型中应解决的液体复苏和抗生素治疗建议。与人类脓毒症类似，除非是研究的一部分，否则建议在实验环境中进行液体复苏。建议使用等渗晶体溶液。给药途径及其时间应根据模型的具体要求进行调整，优先考虑动态而不是静态血流动力学监测。应考虑定义液体复苏的终点并避免液体超负荷。临床前脓毒症研究在抗生素方案的使用上存在严重的不一致。为了解决这个问题，建议在临床前研究中使用抗生素，并根据特定的脓毒症模型和病原体（s）选择和调整剂量。理想情况下，抗生素的给药应模拟临床实践，考虑到药物的药代动力学特征、吸收、分布和清除的改变，以及年龄、体重和合并症等宿主因素。这些建议和注意事项被提议作为临床前脓毒症动物模型的“最佳实践”，应予以实施。
