肾功能不全及行连续性肾脏替代治疗患者的替考拉宁血药浓度监测及优化给药方案研究

目的：评估肾功能不全及行连续性肾脏替代治疗（continuous renal replacement therapy，CRRT）患者给予替考拉宁高负荷剂量用药方案的谷浓度水平，以及CRRT对其清除的影响。方法：前瞻性收集南京医科大学附属苏州医院2018年6月至2021年1月重症监护室使用替考拉宁抗感染治疗的肾功能不全肌酐清除率≤50 mL·min^-1·（1.73 m）^-2]患者，分为CRRT （CVVH模式）组和非CRRT组，给予高负荷剂量8~10 mg·kg^-1，q12h×3剂。在替考拉宁给药第3剂及第6~8剂前测定血清谷浓度，CRRT组同时测定滤出液浓度，并计算替考拉宁滤过系数。结果：共纳入46例患者，给予替考拉宁高负荷剂量后，非CRRT组和CRRT组的第3剂前血清谷浓度达标率分别为79.17%和86.36%，第6~8剂前谷浓度达标率分别为83.33%和90.91%。用药前白蛋白水平<30 g·L^-1的替考拉宁第3剂及第6~8剂前谷浓度显著低于白蛋白≥30 g·L^-1组11.88（8.99，14.26） mg·L^-1 vs.16.92（12.46，24.30） mg·L^-1，P=0.024；12.42（11.84，14.55） mg·L^-1 vs.20.2（12.42，24.18） mg·L^-1，P=0.007]。CRRT患者超滤率为（46.66±12.72） mL·kg^-1·h，测定替考拉宁血药谷浓度和同时间点的滤出液浓度分别为：18.08（11.99，24.18） mg·L^-1和（3.49±1.09） mg·L^-1，替考拉宁滤过系数为0.180±0.049。结论：肾功能不全及行CRRT的危重症感染患者在替考拉宁高负荷剂量给药方案下可快速达到谷浓度目标范围，血清白蛋白水平明显影响替考拉宁血清谷浓度。

Study on serum concentration monitoring and optimal administration of teicolanin in critical ill CRRT patients

OBJECTIVE To evaluate the trough concentration level of teicoplanin in patients with renal insufficiency and continuous renal replacement therapy (CRRT), and effect of CRRT on the clearance of teicoplaninin CRRTpatients.METHODS Patients with renal insufficiencycreatinine clearance rate ≤ 50 mL·min^-1·(1.73 m^-2)] receiving teicoplanin treatment in the ICU of Suzhou Hospital Affiliated to Nanjing Medical University from June 2018 to January 2021 were prospectively collected, divided into CRRT (CVVH mode) group and renal insufficiency group. All patients were given three high-loading doses of 8-10 mg·kg^-1,q12h. Trough concentrations were measured before the 3rd dose and 6th-8th dose of teicoplanin. The filtrate concentration of the CRRT group was measured at the same time, and the filtration coefficient of teicoplanin was calculated.RESULTS A total of 46 patients were included. After given high loading doses of teicoplanin, the rates of trough concentration before the third dose in the target range were 79.17% and 86.36% in the non-CRRT group and CRRT group,, 83.33% and 90.91% before the sixth to eighth dose, respectively. The trough concentrations of the third and sixth to eighth doses of teicoplanin with albumin level < 30 g·L^-1 before administration were significantly lower than those of the group with albumin level ≥ 30 g·L^-111.88(8.99,14.26) mg·L^-1 vs. 16.92(12.46,24.30) mg·L^-1, P=0.024;12.42 (11.84,14.55) mg·L^-1 vs. 20.2(12.42,24.18) mg·L^-1, P=0.007]. The ultrafiltration rate of CRRT patients was (46.66±12.72) mL·kg^-1·h. The trough concentration of teicoplanin blood and the filtrate at the same time were 18.08(11.99, 24.18) mg·L^-1 and (3.49±1.09) mg·L^-1, respectively. The filtration coefficient of teicoplanin was 0.180±0.049.CONCLUSION In critical ill patients with renal insufficiency and CRRT, teicoplanin can quickly reach the target range of serum trough concentration when given high-loading doses. Serum albumin level can significantly affect teicoplanin trough concentration.