重症患者万古霉素血药浓度影响因素的研究

发布时间：2018-04-15 07:07

本文选题：重症患者 + 万古霉素　；参考：《吉林大学》2017年硕士论文

【摘要】：目的:重症患者万古霉素血清药物浓度的影响因素复杂多样,肾功能正常与否、血浆蛋白水平等均可影响万古霉素的药代动力学。本研究旨在分析不同肾功能及其病理状态下万古霉素的代谢特点,探讨重症患者万古霉素药代动力学的影响因素及给药方案。方法:选取吉林大学第二医院2016年01月至2016年12月入住ICU病房使用万古霉素治疗的重症感染患者,收集患者的性别、年龄、身高、体重、APACHEⅡ评分、血肌酐值、胱抑素C、白蛋白,尿量、万古霉素给药量、血清谷浓度等指标。根据肌酐清除率水平分为肾功能正常组(CCr≥60ml/min·1.73m2)及肾功能减退组(CCr60ml/min·1.73m2),再根据万古霉素血清谷浓度水平分为谷浓度10mg/L组、谷浓度10~20mg/L组及谷浓度20mg/L组,分析不同肾功能及不同血清谷浓度组年龄、白蛋白、尿量、胱抑素C、CCr、给药量及APACHEⅡ评分的差别及对谷浓度的影响。结果:肾功能减退组有40.91%(9次)万古霉素血清谷浓度10mg/L,27.27%(6次)血清谷浓度在10~20mg/L之间,31.82%(7次)血清谷浓度20mg/L;肾功能正常组有50.00%(12次)万古霉素血清谷浓度10mg/L时,37.50%(9次)血清谷浓度在10~20mg/L之间,12.50%(3次)血清谷浓度20mg/L。肾功能减退组年龄、胱抑素C、APACHEⅡ评分高于肾功能正常组,且差异有统计学意义(t_(年龄)=-1.31,P_(年龄)=0.198;t胱抑素C=-5.68,P胱抑素C=0.000;t APACHEⅡ=-2.79,P APACHEⅡ=0.008);肾功能减退组白蛋白、尿量、给药量均低于肾功能正常组,并有统计学差异(t_(白蛋白)=2.63,P_(白蛋白)=0.011;t_(尿量)=2.63,P_(尿量)=0.012;t_(给药量)=5.07,P_(给药量)=0.000)。肾功能减退组的万古霉素平均谷浓度水平较肾功能正常组高,但二者差异无统计学意义(t_(谷浓度)=-1.13,P_(谷浓度)=0.263)。肾功能减退时不同谷浓度组实际给药量与推荐给药量无明显差别,肾功能正常时不同谷浓度组的实际给药量与推荐剂量也无统计学差异。肾功能减退时谷浓度10mg/L组白蛋白大于谷浓度10~20mg/L组,胱抑素C小于谷浓度10~20mg/L组(t_(白蛋白)=4.37,P_(白蛋白)=0.001;t胱抑素C=-2.83,P胱抑素C=0.014),肌酐清除率无明显差异(t CCr=0.58,PCCr=0.574);谷浓度20mg/L组与谷浓度10~20mg/L组相比,蛋白与胱抑素C有差异(t_(白蛋白)=3.56,P_(白蛋白)=0.004;t胱抑素C=-2.35,P胱抑素C=0.039),肌酐清除率无统计学差异(t CCr=1.08,PCCr=0.303);肾功能正常时谷浓度10mg/L组与谷浓度10~20mg/L组相比尿量存在显著差异(t_(尿量)=2.29,P_(尿量)=0.034),年龄、白蛋白、胱抑素C、CCr及APACHEⅡ评分均无明显差异(t_(年龄)=-1.09,P_(年龄)=0.290;t_(白蛋白)=0.24,P_(白蛋白)=0.813;t胱抑素C=-1.33,P胱抑素C=0.198;t CCr=1.15,PCCr=0.262;t APCHEⅡ=-0.46,P APACHEⅡ=0.650);谷浓度20mg/L组与谷浓度10~20mg/L组相比年龄、白蛋白、尿量、胱抑素C、CCr及APACHEⅡ评分均无统计学差异(t_(年龄)=-0.56,P_(年龄)=0.586;t_(白蛋白)=0.11,P_(白蛋白)=0.916;t_(尿量)=-0.21,P_(尿量)=0.835;t胱抑素C=-0.98,P胱抑素C=0.350;t CCr=-0.37,PCCr=0.717;t APACHEⅡ=-0.02,P APACHEⅡ=0.982)。将影响万古霉素血清谷浓度的因素进行多重线性回归分析结果显示:尿量、CCr及给药量对万古霉素血清谷浓度的影响有统计学意义(t_(尿量)=-2.90,P_(尿量)=0.006;t CCr=-0.092,PCCr=0.005;t_(给药量)=3.859,P_(给药量)=0.000),而年龄、白蛋白、胱抑素C、APAHCEⅡ评分均无统计学意义。结论:1.在肾功能减退时,低白蛋白可导致万古霉素血清谷浓度升高;在肾功能正常时,尿量与万古霉素谷浓度呈负相关。2.肌酐清除率、给药量、尿量均对万古霉素的谷浓度有影响,重症患者应用万古霉素治疗时,在达到稳定的治疗药物浓度前,应前移首次血药浓度监测时间,增加血药浓度监测频率。
[Abstract]:Objective: the influencing factors of patients with severe vancomycin serum concentration of complicated renal function is normal or not, the level of plasma protein can influence the pharmacokinetics of vancomycin. The purpose of this study is to analyze the metabolic characteristics of different renal function and pathological state of vancomycin, and to explore the influencing factors of patients with severe vancomycin pharmacokinetics and dosing regimen.: the second hospital of Jilin University were selected from 2016 01 to December 2016 admitted to the ICU ward using vancomycin in the treatment of severe infection, collect the patient's gender, age, height, body weight, APACHE score, serum creatinine, Cystatin C, albumin, urine volume, vancomycin dosage, serum concentration and other indicators. According to creatinine clearance rate divided into normal renal function group (CCr = 60ml/min, 1.73m2) and renal dysfunction group (CCr60ml/min, 1.73m2), according to the trough serum vancomycin concentration The level of 10mg/L group was divided into the valley, valley concentration in 10~20mg/L group and 20mg/L group of different concentration, renal function and serum concentration of different age group, albumin, urine volume, serum cystatin C, CCr dosage and APACHE score difference and the influence of the valley concentration. Results: renal dysfunction group 40.91% (9) of vancomycin serum concentration of 10mg/L, 27.27% (6) serum concentration between 10~20mg/L, 31.82% (7) serum concentration of 20mg/L in normal renal function group; 50% (12) of vancomycin serum concentration of 10mg/L, 37.50% (9) serum trough concentration between 10~20mg/L, 12.50% (3) 20mg/L. concentration decreased group renal function serum cystatin C, age, APACHE score higher than that of the normal renal function group, and the difference was statistically significant (t_ (age) =-1.31, P_ (age) =0.198; t P, Cystatin C=-5.68, Cystatin C=0.000; t APACHE P APACHE =0.008 II =-2.79, II); renal function Can decreased group albumin, urine volume, the dosage was lower than that of the normal renal function group, and there was significant difference (t_ (albumin) =2.63, P_ (albumin) =0.011; t_ (=2.63, P_ (urine) urine volume (=0.012); t_ =5.07, P_ dosage) (dose) =0.000) vancomycin. Renal dysfunction group average concentration levels than normal renal function group, but no statistically significant difference between the two groups (t_, =-1.13, P_ (concentration) (Gu Nongdu) =0.263). Renal dysfunction at different dosage and concentration of the actual Valley Group recommended dosage had no significant difference, normal renal function when different the minimum concentration of group dosage and the recommended dose had no significant difference. The decline of renal function when the concentration of 10mg/L group is greater than the valley Valley albumin concentration of 10~20mg/L group, C 10~20mg/L group is less than the minimum concentration of cystatin (t_ (albumin) =4.37, P_ =0.001 t (albumin); cystatin C=-2.83, Cystatin P C=0.014), creatinine clearance rate was no significant the difference (t CCr=0.58, PCCr=0.574); compared with the valley concentration 20mg/L group and 10~20mg/L group concentration, protein and cystatin C difference (t_ (albumin) =3.56, P_ =0.004 t (albumin); cystatin C=-2.35, Cystatin P C=0.039), creatinine clearance rate showed no significant difference (t CCr=1.08, PCCr=0.303); normal renal function concentration 10mg/L group and 10~20mg/L group compared to the amount of urine concentration had significant difference (t_ =2.29, P_ (urine) (urine) =0.034), age, albumin, Cystatin C, there were no significant difference between the CCr and APACHE score (t_ (age) =-1.09, P_ (age) =0.290; t_ (albumin) =0.24, P_ =0.813 t (albumin); cystatin C=-1.33, P t CCr=1.15, Cystatin C=0.198; PCCr=0.262; t APCHE P APACHE =0.650 II =-0.46, II); trough concentration of 20mg/L age group compared with 10~20mg/L group, the minimum concentration of albumin, urine volume, serum cystatin C, were no significant difference between the CCr and APACHE score (t_ (age) =-0.56 P_ (age =0.). 586; t_ (albumin) =0.11, P_ (albumin) =0.916; t_ (=-0.21, P_ urine volume) (urine) =0.835; t cystain C=-0.98, P t CCr=-0.37, Cystatin C=0.350; PCCr=0.717; t APACHE P APACHE II =-0.02 II =0.982). Serum concentration of vancomycin will influence factors of multiple linear the results of regression analysis showed that the amount of urine, CCr and dosage of vancomycin serum concentration was statistically significant (t_ =-2.90, P_ (urine) (urine) =0.006; t CCr=-0.092 PCCr=0.005; t_, =3.859, P_ (dose) (dose) =0.000), age, albumin, Cystatin C and the APAHCE score were not statistically significant. Conclusion: 1. in renal insufficiency, low albumin can lead to elevated serum concentration of vancomycin; in normal renal function, urine volume and vancomycin trough concentrations were negatively correlated.2. creatinine clearance rate, dosage, concentration of vancomycin urine were influential, critically ill patients should In the treatment of vancomycin, the monitoring time of the first blood drug concentration should be moved forward before reaching a stable therapeutic drug concentration, and the monitoring frequency of the blood concentration should be increased.

【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R969

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