Department of Intensive Care and Hyperbaric Medicine, The Alfred, Commercial Road, Melbourne, VIC 3004, Australia; Australian and New Zealand Intensive Care Research Centre, Monash University, Commercial Road, Melbourne, VIC 3004, Australia.
Pharmacy Department, Royal Brisbane and Women's Hospital, Butterfield Street, Herston, QLD 4029, Australia; Department of Intensive Care Medicine, Royal Brisbane and Wom en's Hospital, Butterfield Street, Herston, QLD, 4029, Australia; Burns, Trauma, and Critical Care Research Centre, The University of Queensland, Butterfield Street, Herston, QLD 4029, Australia.
Adv Drug Deliv Rev. 2018 Jan 1;123:65-74. doi: 10.1016/j.addr.2017.09.019. Epub 2017 Sep 28.
Patients suffering major burn injury represent a unique population of critically ill patients. Widespread skin and tissue damage causes release of systemic inflammatory mediators that promote endothelial leak, extravascular fluid shifts, and cardiovascular derangement. This phase is characterized by relative intra-vascular hypovolaemia and poor peripheral perfusion. Large volume intravenous fluid resuscitation is generally required. The patients' clinical course is then typically complicated by ongoing inflammation, protein catabolism, and marked haemodynamic perturbation. At all times, drug distribution, metabolism, and elimination are grossly distorted. For hydrophilic agents, changes in volume of distribution and clearance are marked, resulting in potentially sub-optimal drug exposure. In the case of antibiotics, this may then promote treatment failure, or the development of bacterial drug resistance. As such, empirical dose selection and pharmaceutical development must consider these features, with the application of strategies that attempt to counter the unique pharmacokinetic changes encountered in this setting.
大面积烧伤患者是一类特殊的危重症患者。广泛的皮肤和组织损伤会导致全身性炎症介质的释放，从而促进血管内皮通透性增加、血管外液转移和心血管功能紊乱。这一阶段的特点是相对的血管内低血容量和外周灌注不良。通常需要大量静脉补液复苏。此后，患者的临床病程通常会因持续的炎症、蛋白质分解代谢和明显的血流动力学紊乱而变得复杂。在任何时候，药物的分布、代谢和消除都严重扭曲。对于亲水性药物，分布容积和清除率的变化非常明显，导致药物暴露可能不理想。在抗生素的情况下，这可能会导致治疗失败或细菌耐药性的发展。因此，经验性剂量选择和药物开发必须考虑到这些特征，并应用试图对抗这一环境中遇到的独特药代动力学变化的策略。
