万古霉素血药谷浓度监测在ICU患者中的应用

The application of monitoring vancomycin serum trough concentration in ICU patients

[摘要]目的通过监测ICU患者万古霉素血药谷浓度，分析万古霉素血药谷浓度的分布情况、影响血药谷浓度的因素、临床疗效和不良反应。方法采用前瞻性研究方法，选择2012—11—2015—05收住本院内科ICU，确诊或疑诊为革兰阳性菌感染，选择万古霉素治疗并监测其血药谷浓度的患者106例，根据内生肌酐清除率分为A组（肌酐清除率≥50mL／min）和B组（肌酐清除率〈50mL／min），根据《万古霉素临床应用中国专家共识》（2011年）推荐给药，于第四次给药前30min采血送检谷浓度，采用酶放大免疫法测定万古霉素血药浓度，同时收集临床资料，分析万古霉素血药谷浓度的分布情况、影响血药谷浓度的因素、临床疗效、微生物清除率和不良反应的发生概率。结果共纳入合格病例106例，其中A组46例，B组60例。A组和B组血药谷浓度达10～20mg／L比率分别为63．0％和55．0％，〈10mg／L比率分别为26．1％和18．3％，〉20mg／L比率分别为10．9％和26．7％，两组比较差异有统计学意义（P〈0．05）。多重线性回归分析显示，年龄（OR=0．962，95％CI为0．917～1．016，P=0．025）、体质量（OR=1．008，95％CI为0．934～1．071，P=0．033）、血清白蛋白水平（OR=1．102，95％CI为1．024～1．203，P=0．028）、内生肌酐清除率（OR=1．006，95％CI为0．992—1．013，P=0．000）和给药剂量（OR=0．715，95％CI为0．238～1．260，P=0．008）是影响万古霉素血清谷浓度的主要因素。根据血清谷浓度调整万古霉素剂量后，两组患者达到目标谷浓度的时间（3．84-1．9）dVS（4．0±2．5）d）、临床有效率（78．3％VS80．0％）、微生物清除率（88．9％VS87．0％）及不良反应发生率（6．5％VS6．7％）比较差异无统计学意义（P〉0．05）。结论根据2011年专家共识推荐剂量给药后仍有一半以上的患者不能达到目标谷浓度（10-20mg／L），年龄、体质量、血清白蛋白水平、肌酐清除率及给药剂量是影响谷浓度的主要因素；经个体化给药后，不同肾功能状态的患者仍可达到相同的临床疗效而避免增加不良反应的发生率。

Objective To analyze the distribution of serum trough concentration, related factors, clinical efficacy and adverse reactions, by monitoring vancomyc in serum trough concentration in ICU patients. Methods A prospective study was conducted. Data of 106 patients who used vancomycin during December 2012 to May 2015 in medical intensive care unit （MICU） of the Lanzhou University Second Hospital, were collected and analyzed. According to the endogenous creatinine clearance rate （CCr） , the patients were divided into two groups： A group （CCr~〉50 mL/min） and B group （CCr 〈 50 mL/min）. Thirty minutes before the forth dose, recommended by Chinese Expert Consensus for clinical application of vancomycin, blood samples were collected to determine the trough blood concentration by enzyme- multiplied immunoassay technique. The clinical data were collected at the same time. The distribution of vancomyc in serum trough concentration, factors affecting serum trough concentration, efficacy and adverse reactions between two groups were analyzed. Results A total of 106 patients were in accordance with the inclusive criteria, of which 46 patients in group A and 60 patients in group B. In group A, 63.0% of them reached the targeting serum trough concentration （10 ~20 mg/L）, 26.1% of them 〈 10 mg/L and 10.9% of them 〉 20 mg/L. In group B, 55.0% of them reached the target concentration（ 10 -20 rag/L）, 18.3% of them 〈 10 mg/L and 26.7% of them 〉 20 mg/L. Between group A and group B, the distribution of vancomycin serum trough concentration was significantly different（P 〈0.05）. Age（ OR =0. 962, 95% CI 0. 917 ~ 1. 016,P =0. 025）, weight（ OR = 1. 008, 95% CI 0.934 ~ 1. 071, P = 0.033）, serum albumin level（ OR = 1. 102, 95% CI 1. 024 - 1. 203, P = 0. 028）, endogenous creatinine clearance rate（ OR = 1. 006, 95% CI 0.992 - 1. 013, P = 0.000） and vancomycin doses（ OR = 0. 715, 95% CI 0. 238 ~ 1. 260, P = 0. 008 ） were found to be correlated to serum trough concentration by multiple linear regression analysis. After adjustment of vancomycin dosages according to serum trough concentration, there were no significant differences in times took to reach target trough concentration, efficacy and adverse reactions （ P 〉 0.05 ）. Conclusion Though achieving the recommended doses by Chinese Expert Consensus in 2011, vancomycin serum trough concentration of some patients cannot reach target concentration （10 ~ 20 mg/L）. Age, weight, serum albumin level, endogenous creatinine clearance rate and vancomycin doses show relatively significant influences to serum trough concentration. After individualized dosing, patients with different renal function can still achieve the same efficacy and avoid aggravating adverse reactions.