Critical Care Department, University Hospital Vall d’Hebron, Vall d’Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona Spain.
Curr Pharm Biotechnol. 2011 Dec;12(12):1996-2001. doi: 10.2174/138920111798808365.
Despite the importance of early an appropriate therapy for the outcomes of severe infections in critically ill patients, there is still little understanding of dose optimization during the most important phase of the treatment, the initial phase. Disease-driven variations in pharmacokinetics and pharmacokinetics/ pharmacodynamics may compromise the therapeutic success of antibiotic therapy. Therefore, dose adjustments that account for these variations are paramount for improving antibiotic use in critically ill patients. Compelling evidence shows significant increases in the Vd of both hydrophilic and lipophilic drugs in critically ill patients as a consequence of patient pathology and from clinical interventions. These increases in the Vd can lead to lower than expected plasma concentrations during the first day of therapy, which may result in sub-optimal achievement of antibiotic pharmacokinetics/pharmacodynamic targets, resulting in inappropriate treatment. Therefore, loading doses of antibiotic during the first day of therapy that account for the predicted increase in the Vd are required. Further research towards the establishment of new dosing regimens that use loading doses to satisfy such increased volumes of distribution is recommended.
尽管在危重病患者中严重感染的早期适当治疗对其结局非常重要，但对于治疗的最重要阶段（初始阶段）的剂量优化仍知之甚少。疾病驱动的药代动力学和药代动力学/药效学变化可能会影响抗生素治疗的成功。因此，为了改善危重病患者的抗生素使用，必须进行考虑这些变化的剂量调整。有强有力的证据表明，由于患者病理和临床干预，危重病患者的亲水性和疏水性药物的 Vd 均显著增加。Vd 的增加可导致治疗的第 1 天的血浆浓度低于预期，这可能导致抗生素药代动力学/药效学目标无法达到最佳，从而导致治疗不当。因此，需要在治疗的第 1 天使用负荷剂量的抗生素，以考虑到 Vd 的预计增加。建议进一步研究使用负荷剂量来满足这种分布容积增加的新剂量方案。
