注射用丹参（冻干）不良反应的临床特征及预警信号探讨

Exploration of the clinical characteristics of adverse reactions and warning signals of Danshen lyophilized powder injection

目的探讨注射用丹参（冻干）不良反应的临床特征及预警信号。方法收集山东省药品不良反应监测中心数据库2005年1月1日至2015年12月31日接收的注射用丹参（冻干）ADR报告，采用描述性统计方法分析ADR临床特征，采用比例报告比（PRR）法、报告比值比（ROR）法和贝叶斯判别可信区间递进神经网络模型（BCPNN）法对2005至2015年的ADR总体数据和每个年度的数据进行分析，挖掘ADR预警信号。结果纳入分析的ADR报告为887份，所涉及的887例患者中男性460例，女性427例；年龄3d～91岁，平均（57．7±16．6）岁，≥45岁者占79．59％（706／877）。887例患者共发生1281例次ADR，主要累及皮肤和心脑血管系统，排序前10位者依次为皮疹、瘙痒、呼吸困难、寒战、恶心、头痛、发热、心悸、头晕和注射部位反应，共1152例次，占89．93％。出现ADR后均停用注射用丹参（冻干），经对症治疗后557例痊愈，330例好转。应用PRR法、ROR法和BCPNN法对ADR总体数据和年度数据进行分析的结果显示，皮疹（PRR法：总体数据，2008至2015年；ROR法：总体数据，2008至2014年；BCPNN法：总体数据）、瘙痒（PRR法：总体数据，2012、2013、2015年；ROR法：总体数据，2012、2013年）、呼吸困难（PRR法：总体数据，2008至2014年；ROR法：总体数据，2008至2014年；BCPNN法：总体数据，2014年）、寒战（PRR法：总体数据，2007至2009年；ROR法：总体数据，2011至2013年；BCPNN法：总体数据，2012、2013年）可作为注射用丹参（冻干）的ADR预警信号。结论注射用丹参（冻干）所致ADR主要累及皮肤和心脑血管系统，皮疹、瘙痒、呼吸困难、寒战可作为注射用丹参（冻干）ADR发生的预警信号。

Objective To explore the clinical characteristics and the warning signals of Danshen lyophilized powder injection （DLPI）. Methods The adverse drug reaction （ADR） reports of DLPI from the ADR Spontaneous Reporting Database of Shandong Province from January 1,2005 to December 31,2015 were collected. The clinical characteristics of ADR were analzed by descriptive statistical method. The conceptual data and the data for each year from 2005 to 2015 were analyzed to find out the warning signals of ADR induced by DLPI by the methods of proportional reporting ratio （PRR）, reporting odds ratio （ROR）,and bayesian confidence propagation neural network （BCPNN）. Results A total of 887 reports and 887 patients which comprised 460 males and 427 females with the average age of （57.7 ± 16.6） years （3 d to 91 years） were enrolled into the analysis. The patients whose age ≥45 years accounted for 79.59% （706/ 887）. There were 1 281 times of ADR in 887 patients which involved mainly in skin and cardio- cerebrovascular system. Top ten in turn were erythra, pruritus, dyspnea, shiver, nausea, headache, fever, palpitation, dizziness, and injection site reactions, totally 1 152 times of ADR which accounted for 65.89% （ 1 152/1 281 ）. The patients stopped to use DLPI when the ADR appeared. Of the 887 patients, 557 cases were recovered and 330 had improvement after receiving the symptomatic treatments. The results of analysis on conceptual data and the data for each year by methods of PRR, TOR, and BCPNN showed that erythra （PRR method： conceptual data, from 2008 to 2015; ROR method： conceptual data, from 2008 to 2014; BCPNN method： conceptual data）, pruritus （PRR method： conceptual data, 2012, 2013, 2015; ROR method： conceptual data, 2012, 2013）, dyspnea （PRR method： conceptual data, from 2008 to 2014; ROR method： conceptual data, from 2008 to 2014; BCPNN method： conceptual data, 2014） , shiver （PRR method： conceptual data, from 2007 to 2009; ROR method： conceptual data, from 2011 to 2013; BCPNN method：conceptual data, 2012 and 2013） could be warning signals of ADR induced by DLPI. Conclusions ADRs due to DLPI involve mainly skin and cardio-cerebrovascular system. Erythra, pruritus, dyspnea, and shiver can be the warning signals of ADR induced by DLPI.