连续肾脏替代治疗重症感染患者多黏菌素B血药浓度监测与PK/PD研究

    Monitoring of Polymyxin B Blood Concentrations and PK/PD Studies in Critically Ill Patients with Severe Infection Undergoing Continuous Renal Replacement Therapy

    • 摘要:
      目的 分析行连续性肾脏替代治疗(continuous renal replacement therapy,CRRT)患者和未行CRRT患者多黏菌素B血药浓度和疗效,评估CRRT对多黏菌素B清除的影响,为临床合理使用多黏菌素B提供参考依据。
      方法 采用前瞻性研究方法对68例重症感染患者(CRRT组16例,非CRRT组52例)接受多黏菌素B静脉滴注48 h后的血药浓度(包括谷浓度、峰浓度、6 h浓度以及10 h浓度)进行分析,收集2组患者的临床资料(性别、年龄、体质量、血清肌酐、白蛋白、感染类型、细菌学情况等),通过组间差异性检验评估CRRT对多黏菌素B血药浓度的影响并探究血药浓度与临床疗效及不良反应之间的关系。
      结果 CRRT组AUC0-24 hCminCmaxC6C10分别为(72.85±26.02)mg·h·L−1、(1.67±0.86)mg·L−1、(6.22±2.64)mg·L−1、(2.45±0.94)mg·L−1、(1.89±1.24)mg·L−1;非CRRT组AUC0-24 hCminCmaxC6C10分别为(77.99±37.11)mg·h·L−1、(1.75±1.35)mg·L−1、(6.26±2.72)mg·L−1、(2.43±1.19)mg·L−1、(1.79±1.17)mg·L−1。2组的CminCmaxC6C10及AUC0-24 h差异均没有统计学意义。临床疗效方面,非CRRT组患者无效组和有效组多黏菌素B AUC0-24 h<50 mg·h·L−1的比例分别为17.4%和27.6%,AUC0-24 h在50~100 mg·h·L−1的分别为60.9%和44.8%,AUC0-24 h≥100 mg·h·L−1的分别为21.7%和27.6%,差异无统计学意义;CRRT组患者无效组和有效组多黏菌素B AUC0-24 h<50 mg·h·L−1的比例分别为11.1%和14.3%,AUC0-24 h在50~100 mg·h·L−1的分别为77.8%和71.4%,AUC0-24 h≥100 mg·h·L−1的分别为11.1%和14.3%,分布比例相似,2组间差异无统计学意义。不良反应方面 ,68例患者中发生不良反应共8例,均在非CRRT组,有5例皮肤色素沉着反应、2例呕吐、1例腹泻,非CRRT组观测到急性肾损伤的发生率为32.69%,发生急性肾损伤与没有发生急性肾损伤的AUC0-24 h差异有统计学意义(P<0.05)。
      结论 CRRT不会降低多黏菌素B的血药浓度,非CRRT组中急性肾损伤发生率较高且与AUC0-24 h相关,在使用多黏菌素B时应进行血药浓度监测,以提高药物临床疗效,减少肾毒性或降低不良反应的发生率。

       

      Abstract:
      OBJECTIVE To analyze the blood concentrations and efficacy of polymyxin B in patients undergoing continuous renal replacement therapy(CRRT) and those not undergoing CRRT, to assess the impact of CRRT on the clearance of polymyxin B, and to provide a reference for the rational use of polymyxin B in clinical practice.
      METHODS A prospective study design was employed to investigate the plasma concentrations of polymyxin B(including trough concentration, peak concentration, 6 h concentration, and 10 h concentration) in 68 critically ill patients(16 in the CRRT group and 52 in the non-CRRT group) following 48 h of intravenous polymyxin B infusion. Clinical data were collected for both groups, including gender, age, weight, serum creatinine, albumin, infection type, bacteriological status, etc., and conducted intergroup difference tests to assess the impact of CRRT on polymyxin B blood concentrations and explore the relationship between blood concentrations and clinical efficacy and adverse reactions.
      RESULTS The CRRT group had AUC0-24 h, Cmin, Cmax, C6, and C10 values of (72.85±26.02)mg·h·L−1, (1.67±0.86)mg·L−1, (6.22±2.64)mg·L−1, (2.45±0.94)mg·L−1, (1.89±1.24)mg·L−1; in the non-CRRT group, the AUC0-24 h, Cmin, Cmax, C6, and C10 values were(77.99±37.11)mg·h·L−1, (1.75±1.35)mg·L−1, (6.26±2.72)mg·L−1, (2.43±1.19)mg·L−1, and (1.79±1.17)mg·L−1, respectively. There were no statistically significant differences between the two groups in terms of Cmin, Cmax, C6, C10, and AUC0-24 h. In terms of clinical efficacy, the proportions of patients in the ineffective and effective groups of the non-CRRT group with polymyxin B AUC0-24 h <50 mg·h·L−1 were 17.4% and 27.6%, respectively; they were 60.9% and 44.8% while AUC0-24 hwere in 50–100 mg·h·L−1, respectively; and they were 21.7% and 27.6% while AUC0-24 h≥100 mg·h·L−1, respectively, with no statistically significant difference. In the CRRT group, the proportions of patients in the ineffective and effective groups with polymyxin B AUC0-24 h <50 mg·h·L−1 were 11.1% and 14.3%, respectively; there were 77.8% and 71.4% while AUC0-24 hwere in 50–100 mg·h·L−1, respectively; and they were 11.1% and 14.3% while AUC0-24 h≥100 mg·h·L−1, respectively. The distribution proportions were similar, and there was no statistically significant difference between the two groups. Adverse reactions: among 68 patients, 8 cases of adverse reactions occurred, all in the non-CRRT group: 5 cases of skin pigmentation reactions, 2 cases of vomiting, and 1 case of diarrhea. The incidence of acute kidney injury in the non-CRRT group was 32.69%. There was a statistically significant difference in AUC0-24 h between patients with acute kidney injury and those without(P<0.05).
      CONCLUSION CRRT does not reduce the blood concentration of polymyxin B. The incidence of acute kidney injury is higher in the non-CRRT group and is associated with AUC0-24 h. Blood concentration monitoring should be performed when using polymyxin B to improve clinical efficacy, reduce renal toxicity or reduce the incidence of adverse reactions.

       

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