连续肾脏替代治疗重症患者多黏菌素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 Undergoing Continuous Renal Replacement Therapy

关键词:  多黏菌素B  重症患者  肾脏替代治疗  PK/PD

Key words:  polymyxin B  critically ill patients  renal replacement therapy  PK/PD

摘要:

目的 分析行连续性肾脏替代治疗(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48h后的血药浓度(包括谷浓度、峰浓度、6h浓度以及10h浓度),收集2组患者的临床资料(性别、年龄、体重、APACHE-Ⅱ评分、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AUCss-24h、Cmin、Cmax、C6、C10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AUCss-24h、Cmin、Cmax、C6、C10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。两组的Cmin、Cmax、C6、C10及AUCss-24h均没有统计学意义(P>0.05)。临床疗效方面 非CRRT组患者无效组和有效组多黏菌素B AUCss-24h在<50mg h L-1组的比例分别为17.4%和27.6%、50-100mg h L-1组分别为60.9%和44.8%和≥100mg h L-1组分别为21.7%和27.6%,差异无统计学意义(P>0.05)；CRRT组患者无效组和有效组多黏菌素B AUCss-24h在<50mg h L-1组的比例分别为11.1%和14.3%,50-100mg h L-1组分别为77.8%和71.4%,≥100组mg h L-1分别为11.1%和14.3%,分布比例相似,两组间差异无统计学意义(P>0.05)。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5例皮肤色素沉积反应、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%,发生急性肾损与没有发生急性肾损的AUCss-24h比较有统计学差异(P<0.05)。结论 CRRT不会降低多黏菌素B的血药浓度,非CRRT组中急性肾损发生率较高且与AUCss-24h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、减少肾毒性等不良反应的发生。

Abstract:

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-hour concentration, and 10-hour concentration) in 68 critically ill patients (16 in the CRRT group and 52 in the non-CRRT group) following 48 hours of intravenous polymyxin B infusion. Clinical data were collected for both groups, including gender, age, weight, APACHE-II score, 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 AUCss-24h, 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; in the non-CRRT group, the AUCss-24h, Cmin, Cmax, C6, and C10 values were (77.99 ± 37.11) mg·h L-1, (1.75 ± 1.35) mg/L, (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 AUCss-24h (P > 0.05). In terms of clinical efficacy, the proportions of patients in the ineffective and effective groups of the non-CRRT group with polymyxin B AUCss-24h in the <50 mg h L-1 group were 17.4% and 27.6%, respectively; in the 50–100 mg h L-1 group, they were 60.9% and 44.8%, respectively; and in the ≥100 mg h L-1 group, they were 21.7% and 27.6%, respectively. with no statistically significant difference (P > 0.05). In the CRRT group, the proportions of patients in the ineffective and effective groups with polymyxin B AUCss-24h in the <50 mg·h?1 group were 11.1% and 14.3%, respectively, 77.8% and 71.4%, respectively, in the 50–100 mg h L-1 group, and 11.1% and 14.3%, respectively, in the ≥100 mg h L-1 group. The distribution proportions were similar, and there was no statistically significant difference between the two groups (P > 0.05). 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 AUCss-24h 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 AUCss-24h. Blood concentration monitoring should be performed when using polymyxin B to improve clinical efficacy and reduce adverse reactions such as nephrotoxicity.