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众所周知的难以管理。由于伤口部位以及更重要的是其他身体部位和重要器官系统发生的解剖学、生理学、激素和免疫学变化的组合，患者表现出显著的变异性。皮肤烧伤除了导致大量体液流失外，还导致多种炎症介质的释放。炎症介质和伤口细菌分布到中枢器官可引起复杂的生理变化，可能导致多器官功能衰竭，约50%的严重烧伤患者发生严重感染。抗生素在烧伤患者体内的分布动力学，如生物利用度、清除率、分布容积、消除半衰期和血浆中的未结合分数可显著改变。如果不详细了解诸如伤口pH、组织氧合、从局部伤口微血管系统泄漏的液体的蛋白质浓度、组织结合、水肿以及由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关系，则难以预期局部和全身感染控制治疗的优化。该项目旨在确定烧伤患者的生理变化，特别是在烧伤伤口环境中，如何影响抗生素渗透和分布到组织中。我们还认为，这些变化将因患者而异，旨在确定某些参数是否可用于指示个体患者的最佳抗生素给药方案。

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.