Management of burn injury: Fluid dynamics and antibiotic pharmacokinetics

众所周知，严重烧伤，以及相对常见的伤害，是出了名的难以处理。患者表现出显著的变异性，这是由于在伤口部位以及更重要的身体其他部分和重要器官系统都发生了解剖学、生理学、激素和免疫学变化。皮肤烧伤导致多种炎症介质的释放，此外还有大量的液体丢失。炎症介质和创面细菌在中枢器官的分布可引起复杂的生理变化，可能导致多器官衰竭，约50%的严重烧伤患者会发生严重感染。烧伤患者体内抗生素分布动力学，如生物利用度、清除量、分布体积、消除半衰期和游离分数等均可显著改变。如果不详细了解伤口pH值、组织氧合、局部创面微血管渗漏的液体蛋白浓度、组织结合、水肿以及复苏治疗引起的烧伤和非烧伤组织的变化等因素之间的变化和相互关系，局部和全身感染控制治疗的优化很难取得进展。该项目旨在确定烧伤患者的生理变化，特别是烧伤创面环境中的变化，如何影响抗生素在组织中的渗透和分布。我们还认为，这些变化将因患者而异，目的是确定是否可以使用某些参数来指示个别患者的最佳抗生素剂量方案。

It is well known that major burns, as well as being relatively common injuries, are notoriously difficult to manage. Patients exhibit significant variability due to a combination of anatomic, physiologic, hormonal and immunologic alterations occurring both at the wound site and, more importantly, in other body compartments and vital organ systems. Skin burn injury results in the release of multiple inflammatory mediators in addition to significant fluid loss. The distribution of inflammatory mediators and wound bacteria to central organs can cause complex physiological changes that may lead to multiple organ failure, with serious infections occurring in around 50% of patients with serious burns. Antibiotic distribution kinetics, such as bioavailability, clearance, volume of distribution, elimination half-life and unbound fraction in plasma can be significantly altered in burn patients. Without detailed knowledge of changes and relationships between factors such as wound pH, tissue oxygenation, protein concentrations of fluid leaked from the local wound microvasculature, tissue binding, oedema and changes in burned and non-burned tissue induced by resuscitation therapies, the optimisation of both local and systemic infection contriol therapies can hardly be expected to advance. This project aims to determine how changes the physiology of burn patients, in particular in the burn wound environment, affect antibiotic penetration and distribution into tissues. We also believe that these changes will vary between patients and are aiming to determine whether certain parameters can be used to give an indication of the best antibiotic dosing regimens for individual patients.