Department of Clinical, Social, and Administrative Sciences, College of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, MI 48109-1065, USA.
Nat Rev Nephrol. 2011 Apr;7(4):226-35. doi: 10.1038/nrneph.2011.12. Epub 2011 Feb 22.
A common cause of acute kidney injury (AKI) is sepsis, which makes appropriate dosing of antibiotics in these patients essential. Drug dosing in critically ill patients with AKI, however, can be complicated. Critical illness and AKI can both substantially alter pharmacokinetic parameters as compared with healthy individuals or patients with end-stage renal disease. Furthermore, drug pharmacokinetic parameters are highly variable within the critically ill population. The volume of distribution of hydrophilic agents can increase as a result of fluid overload and decreased binding of the drug to serum proteins, and antibiotic loading doses must be adjusted upwards to account for these changes. Although renal elimination of drugs is decreased in patients with AKI, residual renal function in conjunction with renal replacement therapies (RRTs) result in enhanced drug clearance, and maintenance doses must reflect this situation. Antibiotic dosing decisions should be individualized to take into account patient-related, RRT-related, and drug-related factors. Efforts must also be made to optimize the attainment of antibiotic pharmacodynamic goals in this population.
急性肾损伤 (AKI) 的一个常见病因是败血症，这使得在这些患者中适当给予抗生素剂量至关重要。然而，患有 AKI 的危重症患者的药物剂量可能会变得复杂。与健康个体或终末期肾病患者相比，危重症和 AKI 都会显著改变药代动力学参数。此外，在危重症人群中，药物药代动力学参数具有高度可变性。亲水性药物的分布容积会因液体超负荷和药物与血清蛋白结合减少而增加，因此必须向上调整抗生素的负荷剂量以适应这些变化。尽管 AKI 患者的药物肾脏清除率降低，但残余肾功能结合肾脏替代治疗 (RRT) 会导致药物清除率增强，因此必须调整维持剂量以反映这种情况。抗生素剂量决策应个体化，以考虑患者相关、RRT 相关和药物相关因素。还必须努力优化该人群中抗生素药效学目标的实现。
