摘要
目的了解双黄连注射剂不良反应(ADR)在不同年龄、系统和严重程度的分布、构成及影响因素,为双黄连注射剂临床合理应用和上市后再评价提供参考。方法计算机检索中国期刊全文数据库(CNKI,1979.1～2009.9)、中国科技期刊全文数据库(VIP,1989.1～2009.9)和中国生物医学文献数据库(CBM,1978.1～2009.9),按纳入与排除标准选择文献、提取资料,并按不同类别(年龄、过敏史、涉及系统、联合用药等)计算出双黄连注射剂ADR总数、构成比,根据临床研究中可获得的用药人数与ADR病例数估算ADR发生率。结果①共纳入452篇文献,合计2799例ADR病例,近20年发表文献以病例报告为主(84.51%),根据69篇文献报告的31165例用药人数和1013例ADR数,计算出ADR总发生率为3.25%。②ADR病例中男女比例为1.13?1,18岁以下未成年人占32.71%。③ADR病例药物过敏史以青霉素最多(占13.38%),其次为磺胺、头孢菌素、喹诺酮类等。④ADR病例原患疾病中呼吸系统占91.75%,其次为消化系统(5.17%)、泌尿系统(1.11%)等。⑤药物联用以青霉素最多,发生ADR的风险是单用的3.14倍[95%CI(2.58,3.81)]。⑥ADR涉及全身多个系统和器官,构成比由高到低依次为皮肤、消化系统、全身反应、呼吸系统、神经系统、心血管系统、局部反应、泌尿系统、血液系统及其它。⑦按WHO药物ADR严重程度分级,Ⅰ、Ⅱ、Ⅲ、Ⅳ级分别占6.36%、5.48%、45.62%、2.12%;52.42%的ADR病例未描述具体临床表现与转归。⑧12例死亡病例除1例因疼痛诱发心肌梗死致死外,其余均因过敏性休克致死,2例曾合并用药,ADR出现最快者1分钟内。⑨双黄连粉针剂ADR发生率(2.25%)低于注射液(4.14%),其差异有统计学意义。结论双黄连注射剂ADR临床表现以皮肤过敏和消化道反应为主,联合用药会增加ADR风险,粉针剂比注射液安全性高。建议加强对双黄连注射剂从生产到临床应用过程的监管与监测,严格规范ADR报告,分级风险评估与管理ADR。
Objectives To systematically evaluate the clinical characteristics of adverse drug reactions（ADRs） caused by Shuanghuanglian Injection（SHLI） and to provide reference for post-market evaluation and clinical application of SHLI.Methods We searched electronic databases such as the Chinese National Knowledge Infrastructure（CNKI,1979.1-2009.9）,the Chinese Science and Technology Journal Full-text Database（VIP,1989.1-2009.9）,and the Chinese Biomedical Disc（CBMdisc,1978.1-2009.9）.ADR cases were analyzed according to occurrences categorized.Available data was assessed using the Chi-square test including relative ratios（RR） with 95% confidence intervals（95%CI）.Different medicine combinations and comparisons between SHL powder injection and SHL injection were calculated using the statistical software Stata 9.1.Results（1） A total of 452 articles were included with a total of 2 799 ADR cases reported.Case reports were the main design type of included literature,which accounted for 84.51%.According to 31165 cases of SHLI treatment and 1013 corresponding ADRs,the incidence of SHLI ADR was calculated as 3.25%.（2） The ratio of male to female in the reported ADR cases was 1.13：1.（3） Allergy to Penicillin,which accounted for 13.38% of the total cases,was at the top for past allergic history,followed by sulfonamides and asthma（2.68%）.（4） In terms of disease treated respiratory disease accounted for 91.75% of all cases of SHLI ADRs,followed by digestive diseases（5.17%）,and urinary diseases（1.11%）.（5） Penicillins were the most common combination choice with SHLI,and such combination showed higher ADR risk than SHLI used alone [RR=3.14,95%CI（2.58,3.81）].（6） Multiple systems/organs were involved in SHLI ADRs,and were ranked downwards according to proportion as：skin,digestive system,general reactions,respiratory system,nervous system,cardiovascular system,local reactions,urinary system,hematologic system and others.（7） According to the WHO ADR Classi cation Criteria,ADR cases were divided into four grades.There were 6.36%,5.48%,45.62%,and 2.12% cases of Grade Ⅰ,Ⅱ,Ⅲ and Ⅳ,respectively.And the prognoses of the rest 52.42% cases were reported unclearly.（8） All cases of death were caused by allergic shock,except for one,which was caused by myocardial infarction induced by pain at the injection site.The fastest ADR case occurred 1 minute after being injected.（9） There was a remarkable difference（P〈0.05） in the rate of ADR caused by SHLI in power form（2.25%） and as a solution（4.14%）.Conclusion The clinical manifestations of ADRs caused by SHLI mainly include skin allergic reactions and gastrointestinal reactions.There is an increased risk of ADR induced by combined uses of SHLI and other drugs,especially antibiotics.Compared to the solution,the powder has lower ADR occurrence and higher safety with statistical signi cance.We propose strengthening management and surveillance on SHLI from manufacturing to application,and improving the level of the risk management for post-market drugs.
出处
《中国循证医学杂志》
CSCD
2010年第2期140-147,共8页
Chinese Journal of Evidence-based Medicine
关键词
双黄连注射剂
药物不良反应
文献评价
Shuanghuanglian injection
Adverse drug reaction
Systematic review
