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住院患者使用利奈唑胺致相关性血小板减少症的危险因素分析

局部浓度太高引起。

因此在达到一定浓度时产生浑浊的配伍,而在低浓度时虽然肉眼没有看见浑浊,但是有没有产生对人体有危害的物质,有待于作进一步的研究。

3.3辅料的影响PPC注射液说明书的用法用量一栏中,明确记录严禁用电解质溶液稀释,但许多常用注射液的辅料中均含有电解质,如胃复安注射液的辅料为:浓盐酸、无水醋酸钠、亚硫酸氢钠等。

电解质总量虽然不多,但在局部浓度过高时也可能会影响混合液的性状。

3.3逐步完善药品说明书药品说明书是医护人员和患者了解药品特性、指导医师正确用药、以及评价医师用药是否合理、药师审核处方的重要依据,具有一定的法律效应[6]。

在PPC注射液的药品说明书中虽然明确说明静脉注射时“不可与其他任何注射液混合注射”,但在静脉输注栏中,配伍禁忌可参考的信息太少,没有具体不宜配伍的药品名称,是导致临床频频发生不良配伍事件的主要原因。

因此,针对药物配伍不稳定的文献报道,各药品生产厂家应及时收集验证,并反映到说明书上,以指导临床合理用药,确保患者用药安全有效。

参考文献:[1]刘梅,陆伦根,曾明德.多烯磷脂酰胆碱对肝细胞保护机制的研究进展[J].肝脏,2006,11(1):43-45.[2]蔡爱宁.肝得健与维生素C注射液存在配伍禁忌[J].中国实用护理杂志,2010,26(1):26.[3]陈美花,陆秀英,陈晓蓓.多烯磷脂酰胆碱与4种药物配伍稳定性考察[J].医药导报,2009,28(11):1515-1516.[4]韦曦,刘丽珍.多烯磷脂酰胆碱注射液与几种药物的配伍变化[J].药学服务与研究,2008,8(4):310-312.[5]高敏.多烯磷脂酰胆碱注射液与维生素B6注射液存在配伍禁忌[J].护理研究,2010,24(1):93.[6]温学群.关于药品说明书的调查分析[J].海峡药学,2010,22(10):249-252.(收稿日期:2011-07-17编辑:郭述金)住院患者使用利奈唑胺致相关性血小板减少症的危险因素分析陈超1a郭代红1a*曹秀堂1b蔡云1a王芝林2徐元杰1a朱曼1a马亮1a赵鹏芝1a(1解放军总医院a药品保障中心,b统计科,北京100853;2沈阳药科大学,辽宁沈阳110033)中图分类号:R978;R181.3文献标识码:A文章编号:1672-8629(2012)02-0071-06基金项目:解放军总医院科技创新苗圃基金项目(10KMM41)。

作者简介:陈超,女,学士,主管药师,临床药学。

*通讯作者:郭代红,女,硕士,主任药师,硕士生导师。

E-mail:guodh301@yahoo.com.cn摘要:目的研究住院患者使用利奈唑胺致血小板减少的发生率及危险因素。

方法采用回顾性横断面研究,以解放军总医院2011年1月至2011年5月间使用利奈唑胺的住院患者为研究对象,通过医院信息系统记录患者一般资料、病生理情况、用药情况并动态监测血小板计数变化。

定义血小板减少症为低于正常值下限(即血小板计数<100×109/L),并根据排除标准控制混杂因素,对纳入病例使用利奈唑胺致血小板减少症的观察指标进行逐步逻辑回归筛选危险因素,并绘制ROC曲线预测发生特征。

结果获得用药病例345例,按入排标准纳入有效病例208例,其中男性129(62.02%)例,女性79(37.98%)例,平均年龄为62.67±18.66(16~98)a,用药时间平均为9.68±6.07(3~39)天。

使用利奈唑胺致相关性血小板减少症的有59例(28.37%),发生血小板低于正常值或基础值的25%的有106例(50.96%),其中有20人(9.62%)发生了Ⅲ度和Ⅳ度血小板下降,需要输血或输注血小板。

单因素分析显示年龄、肌酐清除率、基础血小板值、总胆红素、血清白蛋白对血小板减少症的影响具有统计学意义,逐步逻辑回归多因素分析显示基础血小板值和年龄与血小板减少症密切相关。

绘制血ROC曲线Youden指数最大时(0.3855),曲线下面积为0.739时,对应切点的敏感度为62.71%,特异度为75.84%。

结论基础血小板值、年龄是利奈唑胺致相关性血小板减少症的独立危险因素,对基础血小板值≤204×109/L、年龄≥82岁的患者,容易发生明显血小板减少症甚至出血风险,应加强血常规监测频率。

低肌酐清除率、低血清白蛋白水平也是发生血小板减少的重要危险因素,提示利奈唑胺致相关性血小板减少症呈浓度依赖性,并与免疫机制相关。

此外,可尝试使用ROC曲线筛选预测利奈唑胺相关性血小板减少的风险特征,并在易感人群中调整合适剂量以兼顾有效性和安全性。

关键词:利奈唑胺;血小板减少;危险因素,肾功能不全;基础血小板值;ROC曲线;药品不不良反应AnalysisontheRiskFactorsAssociatedwiththeDevelopmentofThrombocytopeniainPatientsWhoReceivedLinezolidTherapyCHEN Chao 1a GUO Dai-hong 1a *CAO Xiu-tang 1b CAI Yun 1a WANG Zhi-lin 2XU Yuan-jie 1a ZHU Man 1a!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!MA Liang1a ZHAO Peng-zhi1a(1a Department of Pharmacy,1b Department of Statistics,the PLA General of Hospital, Beijing100853,China;2Shenyang Pharmaceutical University,Liaoning Shenyang110033,China)Abstract:ObjectiveThis study investigated risk factors associated with the development of thrombocytopenia in patients who received linezolid therapy and to clarify the reasons and incidence of this adverse reaction.MethodsThis was a restrospective study of patients treated with linezolid by the oral or parenteral route,between January 2011and May2011.Data were extracted from the electronic medical records obtained from hospital information system.Thrombocytopenia was defined as a final platelet count of<100×109/L.Risk factors associated with thrombo-cytopenia in patients who received linezolid therapy were identified via logistic regression analysis,and to predict clinical feature via ROC curves.ResultsIn total,208patients(129men and79women;mean[SD]age,62.67[18.66]years[range, 16-98years])were included in the study.The mean duration of linezolid therapy was9.68[6.07]days,with a range of3 to39days.Thrombocytopenia occurred in59patients(28.37%),defined as a decrease in platelet count of≥25%from the baseline occurred in106patients(50.96%).Among the patients,20patients(9.62%)developed severe thrombocytopenia, requiring platelet transfusion.In univariate analysis,age,lowered creatinine clearance,serum albumin,low baseline platelet count,total bilirubin were significant factors for thrombocytopenia associated with linezolid therapy;however, in multivariate analysis,only age,baseline platelet count were significant risk factors for thrombocytopenia associated with linezolid therapy.Draw ROC curves maximum,the curve Youden index for0.739,corresponding area under the sensitivity degrees for62.71%,specific degrees for75.84%.ConclusionBaseline platelet count≤204×109/L,age≥82 years were independent risk factors associated with thrombocytopenia in patients who received linezolid therapy and the incidence may increase.Several factors may influence the occurrence of linezolid-induced thrombocytopenia.Further studys are necessary to determine which at-risk patients are candidates for concentation adjustment of linezolid. Furthermore,we can calculate the area under ROC curves to predict these cut off values for risk factors.Keywords:linezolid;thrombocytopenia;risk factor;renal insufficiency;baseline platelet count;ROC curves;adverse drug reaction近年来革兰阳性球菌的耐药日趋严重,耐甲氧西林金黄色葡萄球菌(MRSA)在全球广泛流行,虽然糖肽类抗菌药物如万古霉素、替考拉宁等一直是治疗革兰阳性菌感染的有效药物,但已出现耐万古霉素肠球菌(VRE)和耐万古霉素金葡菌(VRSA)感染,且其肾毒性一定程度上限制了临床使用。

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