摘要
目的 探讨神经外科重症患者脑脊液万古霉素浓度及其影响因素.方法 采用回顾性研究,选择2016年1月至2019年6月在中山大学附属第一医院重症医学科(ICU)神经外科ICU住院,接受万古霉素治疗并行脑脊液万古霉素浓度监测的成人患者.收集患者一般资料、万古霉素用药方案、脑脊液万古霉素浓度及标本来源、采样前24 h脑脊液引流方式及引流量、合并用药等.分析有无中枢神经系统感染、不同给药方式、给药剂量患者脑脊液万古霉素浓度及其影响因素.结果 共纳入22例患者,送检脑脊液培养标本168份(培养阳性20份,阳性率为11.9%),60例次脑脊液万古霉素浓度监测结果.22例患者中,中枢神经系统感染病原学确诊7例(31.8%),临床诊断11例(50.0%),诊断不确定2例(9.1%),无中枢神经系统感染2例(9.1%);万古霉素单纯静脉用药15例次(25.0%),单纯腰大池给药17例次(28.3%),静脉用药联合腰大池给药23例次(38.3%),静脉用药联合脑室给药5例次(8.3%);脑脊液万古霉素浓度为<0.24~>100 mg/L,中位数14.40(4.79,42.34)mg/L.① 万古霉素给药方式影响脑脊液万古霉素浓度:与单纯静脉用药者相比,腰大池或脑室局部用药者脑脊液万古霉素浓度更高〔mg/L :25.91(11.28,58.17)比2.71(0.54,5.33),U=42.000,P<0.01〕.② 无论是明确中枢神经系统感染(确诊+临床诊断)或是无明确中枢神经系统感染(不确定+无感染),万古霉素单纯静脉给药患者脑脊液万古霉素浓度均较低,分别为4.14(1.40,6.36)mg/L及1.27(0.24,3.33)mg/L,二者差异无统计学意义(U=11.000,P=0.086).③ 随着脑室或腰大池万古霉素给药剂量增加,脑脊液万古霉素浓度增加:治疗药物监测(TDM)前1 d局部万古霉素用量0~15 mg组(22例次)、20~35 mg组(33例次)、40~50 mg组(5例次)脑脊液万古霉素浓度分别为4.14(1.09,8.45)、30.52(14.31,59.61)及59.43(25.51,92.45)mg/L,组间比较差异有统计学意义(H=33.399,P<0.01);脑脊液万古霉素浓度≥10 mg/L的比例分别为18.2%、84.8%及100%;当局部给药剂量≥20 mg/d时,脑脊液万古霉素浓度基本达标.结论 万古霉素单纯静脉用药,无论是否有中枢神经系统感染,神经外科重症患者脑脊液万古霉素浓度难以达到目标水平;局部用药可显著提高脑脊液万古霉素浓度.
Objective To evaluate cerebrospinal fluid(CSF)vancomycin concentrations and identify factors influencing CSF vancomycin concentrations in critically ill neurosurgical patients.Methods A retrospective study was conducted.Adult patients who received vancomycin treatment and CSF vancomycin concentrations monitoring admitted to neurosurgical intensive care unit(ICU)of the First Affiliated Hospital of Sun Yat-sen University from January 2016 to June 2019 were enrolled.General information,vancomycin dosing regimens,CSF vancomycin concentrations,CSF drainage methods and volume of the previous day,and concurrent medications,etc.were collected for analysis.CSF vancomycin concentrations of patients with definite or indefinite central nervous system(CNS)infection,different vancomycin dosing regimens and their influencing factors were analyzed.Results A total of 22 patients were included.168 CSF specimens were collected for culture,20 specimens of which were culture positive,with a positive rate of 11.9%.Sixty cases of CSF vancomycin concentration were obtained.Among the 22 patients,7 patients(31.8%)were diagnosed with proven CNS infection,11 patients(50.0%)clinically diagnosed,2 patients(9.1%)diagnosed with uncertain CNS infection,and 2 patients(9.1%)diagnosed without CNS infection.Intravenous(IV)administration of vancomycin alone was used in 15 cases(25.0%),intrathecal injection in 17 cases(28.3%),IV+intrathecal injection in 23 cases(38.3%),and IV+intraventricular administration in 5 cases(8.3%).The CSF vancomycin concentrations ranged from<0.24 to>100 mg/L,with an average level of 14.40(4.79,42.34)mg/L.①Administration methods of vancomycin affected CSF vancomycin concentrations.The CSF vancomycin concentration with intrathecal injection or intraventricular administration was higher than that of IV administration alone[mg/L:25.91(11.28,58.17)vs.2.71(0.54,5.33),U=42.000,P<0.01].②When vancomycin was administered by IV treatment alone,CSF vancomycin concentrations were low in both groups with definite CNS infection(proven+probable)and indefinite CNS infection(possible+non-infection),the CSF vancomycin concentrations of which were 4.14(1.40,6.36)mg/L and 1.27(0.24,3.33)mg/L respectively,with no significant difference(U=11.000,P=0.086).③CSF vancomycin concentrations rose with the increased dose of vancomycin delivered by intrathecal injection or intraventricular administration.According to the dose of vancomycin administered locally on the day before therapeutic drug monitoring(TDM),cases were divided into the following groups:0-15 mg group(n=22),20-35 mg group(n=33),and 40-50 mg group(n=5),the CSF vancomycin concentrations of which were 4.14(1.09,8.45),30.52(14.31,59.61)and 59.43(25.51,92.45)mg/L respectively,with significant difference(H=33.399,P<0.01).Moreover,the cases of CSF vancomycin concentration of≥10 mg/L accounted for 18.2%,84.8%and 100%of these three groups,respectively.CSF vancomycin concentrations mostly reached target level when dose of vancomycin administered locally were 20 mg/L or more.Conclusions It is difficult to reach target CSF vancomycin concentration for critically ill neurosurgical patients with or without CNS infection by IV treatment.Local administration is an effective treatment regimen to increase CSF vancomycin concentration.
作者
姚明丽
李静超
石磊
李言
王凌雁
管向东
欧阳彬
Yao Mingli;Li Jingchao;Shi Lei;Li Yan;Wang Lingyan;Guan Xiangdong;Ouyang Bin(Department of Critical Care Medicine,the First Affiliated Hospital of Sun Yat-sen University,Guangzhou 510080,Guangdong,China)
出处
《中华危重病急救医学》
CAS
CSCD
北大核心
2019年第10期1252-1257,共6页
Chinese Critical Care Medicine
基金
国家自然科学基金(81801249)
国家临床重点专科建设项目(2011-872)。
关键词
脑脊液
万古霉素
药物浓度
治疗
药物监测
Cerebrospinal fluid
Vancomycin
Drug concentration
Therapy
Therapeutic drug monitoring
