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在危重症儿童中实现连续输注万古霉素的治疗暴露。

Achievement of Therapeutic Vancomycin Exposure With Continuous Infusion in Critically Ill Children.

机构信息

Service de Réanimation et Soins Continus Médico-Chirurgicaux Pédiatrique, AP-HP, Hôpital Necker Enfants-Malades, Paris, France.

Université Paris Descartes, Paris, France.

出版信息

Pediatr Crit Care Med. 2018 Jun;19(6):e263-e269. doi: 10.1097/PCC.0000000000001474.

Abstract

OBJECTIVE

Describe and assess a continuous infusion dosing scheme of vancomycin therapy in critically ill children.

DESIGN

Retrospective single-center study, January to June 2015.

SETTING

PICU located within a French tertiary academic pediatric hospital.

PATIENTS

All children admitted in the PICU from January 2015 to June 2015, receiving continuous infusion of vancomycin therapy.

INTERVENTIONS

None.

MEASUREMENTS AND MAIN RESULTS

Clinical and biological data, vancomycin dosing information, and plasma concentrations were recorded. Using a previously published population pharmacokinetics model, pharmacokinetic parameters were derived for each patient and vancomycin concentrations described after the loading dose. Areas under the curve were estimated for each patient, and an initial covariate-adjusted dose was calculated for every patient. A total of 87 vancomycin concentrations were analyzed from 28 patients between 1 month and 17 years old. The median (range) loading dose was 14.8 (12-16) mg/kg followed by a continuous infusion of vancomycin of 44 (35-61) mg/kg/d. On their first sample, 12 patients (43%) had a concentration between 15 and 30 mg/L. On day 1, the median (range) estimated area under the curve was 349 (201-1,001) mg/L × hr, and seven patients (25%) had an area under the curve greater than 400 mg/L × hr. Using the pharmacokinetics model, the median (range) calculated initial daily dose, taking into account age, bodyweight, and serum creatinine concentration, was 53 (36-69) mg/kg/d resulting in a simulated day 1 area under the curve of 409 (341-593) mg/L × h with a theoretical pharmacokinetic target attainment of 57%.

CONCLUSIONS

The current continuous infusion of vancomycin dosing scheme used in our population was inappropriate and led to underexposure. Using pharmacokinetic approaches such as covariate-adjusted initial dosing and Bayesian estimation of exposure should prove useful for achieving the pharmacokinetic target.

摘要

目的

描述并评估危重症儿童万古霉素持续输注给药方案。

设计

回顾性单中心研究,2015 年 1 月至 6 月。

地点

法国一所三级学术儿童医院的 PICU。

患者

2015 年 1 月至 6 月期间入住 PICU 的所有接受万古霉素持续输注治疗的儿童。

干预

无。

测量和主要结果

记录临床和生物学数据、万古霉素给药信息和血药浓度。使用先前发表的群体药代动力学模型,为每位患者推导药代动力学参数,并描述负荷剂量后的万古霉素浓度。估计每位患者的曲线下面积,并为每位患者计算初始协变量调整剂量。共分析了 28 名 1 个月至 17 岁患者的 87 个万古霉素浓度。负荷剂量中位数(范围)为 14.8(12-16)mg/kg,随后万古霉素持续输注剂量为 44(35-61)mg/kg/d。在第一次取样时,12 名患者(43%)的浓度在 15 至 30mg/L 之间。第 1 天,估计的曲线下面积中位数(范围)为 349(201-1001)mg/L×hr,7 名患者(25%)的曲线下面积大于 400mg/L×hr。使用药代动力学模型,考虑年龄、体重和血清肌酐浓度,计算出的初始每日剂量中位数(范围)为 53(36-69)mg/kg/d,导致模拟第 1 天的曲线下面积为 409(341-593)mg/L×h,理论药代动力学目标达标率为 57%。

结论

我们人群中使用的万古霉素持续输注给药方案目前不合适,导致药物暴露不足。使用药代动力学方法,如协变量调整初始剂量和暴露的贝叶斯估计,对于实现药代动力学目标应该是有用的。

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