万古霉素群体药动学模型在特重度烧伤患者中的临床验证

 目的 评价万古霉素在特重度烧伤患者早期治疗中的临床有效性,为特重度烧伤患者抗感染治疗提供参考。方法 回顾性分析某院重症医学科收治的15例特重度烧伤患者的临床资料,统计分析使用万古霉素治疗的烧伤患者烧伤等级评估、感染指标及血药谷浓度监测结果。采用谷浓度预测和贝叶斯反馈的方法比较目前公开发表的重症患者群体药动学模型,筛选出特重度烧伤患者万古霉素治疗的最适模型,并通过蒙特卡洛模拟,对特重度烧伤患者万古霉素的给药方案进行优化。结果 15例使用万古霉素治疗的患者均采用持续静脉滴注或泵入方式给药,万古霉素平均用药时间为(11.07±1.71) d,79.31%的稳态血药谷浓度达标(10~20 μg/mL),治疗期间有1例患者出现肾毒性。经筛选,选取文献报道的重症患者二房室模型作为特重度烧伤患者万古霉素治疗的最适模型。蒙特卡罗模拟结果显示,24 h持续静脉滴注或泵入给药是万古霉素治疗特重度烧伤患者的最佳给药方式,首剂1.5倍负荷剂量给药可使患者体内万古霉素快速达到有效浓度范围。结论 特重度烧伤患者早期应用万古霉素可有效控制脓毒症。万古霉素持续静脉滴注或泵入,以及足够的负荷剂量,对获得万古霉素最佳治疗效果至关重要。

Clinical verification of vancomycin population pharmacokinetics in patients with extremely severe burn

Objective To evaluate the clinical efficacy of early treatment with vancomycin in extremely severe burned patients, and provide references for anti-infection treatment of patients with extremely severe burn.Methods Clinical data of 15 patients with extremely severe burn and treated in the department of critical care medicine of a hospital were retrospectively analyzed, burn grade evaluation, infection index and trough blood concentration monitoring results of burn patients treated with vancomycin were statistically analyzed. Trough concentration prediction and Bayesian feedback method were adopted to compare the currently published population pharmacokinetic models of severe patients, optimal model for vancomycin treatment in extremely severe burned patients was screened out, administration of vancomycin in severely burned patients was optimized through Monte Carlo simulation.Results All 15 patients were administered vancomycin via continuous intravenous drip or pump, the average time of vancomycin administration was (11.07±1.71) days, and 79.31% of the steady-state trough blood concentrations met the standard (10-20 μg/mL), one patient developed renal toxicity during treatment. After screening, two-compartment model of severe patients reported in literatures was selected as the optimal model for vancomycin treatment in patients with extremely severe burns. Monte Carlo simulation results showed that 24 hours of continuous intravenous drip or pump administration was the best method for vancomycin treatment in patients with extremely severe burn, and the loading dose of 1.5 times of the normal dose can help quickly reach the effective concentration range.Conclusion The development of sepsis in extremely severe burned patients can be well controlled with early application of vancomycin. Continuously drip or pump administration combined with sufficient loading dose are critical to obtain best treatment of vancomycin.