柴胡注射液不良反应或不良事件的系统评价

Adverse drug reactions or adverse events of Chaihu Injection:a systematic review

背景:柴胡注射液是柴胡(Radix Bupleuri Chinensis,又名"北柴胡")或狭叶柴胡(Radix BupleuriScorzonerifolii,又名"南柴胡")经水蒸气蒸馏法制成的水溶液,广泛应用于临床各类发热性疾病的治疗。目的:本研究基于现有证据了解造成柴胡注射液不良反应或不良事件(adverse drug reaction or adverseevent,ADR/AE)的可能原因,并评价其安全性。检索策略:本研究未进行手工检索。电子检索的数据库为中国学术期刊全文数据库(CNKI)和中国科技期刊全文数据库(重庆维普,VIP)。检索时间截止至2009年6月30日。纳入标准:全面收集使用柴胡注射液致ADR/AE的研究,语种和结局指标不限。患者的年龄、性别、种族、原发病不限。干预措施为单独使用柴胡注射液或柴胡注射液与其他药物(含柴胡的中药汤剂或其他制剂除外)联用。资料提取与分析:由两位研究者独立提取资料。采用Microsoft Excel软件制定数据提取表。由于各研究异质性较大,此处仅做描述性分析。结果:本研究共纳入83篇文献203例柴胡注射液ADR/AE。由于无法计算ADR/AE的发生率,因此无法准确评估ADR/AE发生的危险度和柴胡注射液的安全性。研究发现儿童和老人重型病例构成比高于其他年龄段;大部分肌注病例ADR/AE均发生在注射后30 min内(30 min累计发生构成比93.8%);静滴病例的ADR/AE,4例发生在滴注过程中;初次使用者,其ADR/AE 30 min累计发生构成比和重型病例30 min累计发生构成比均高于有柴胡注射液使用既往史的病例。不少柴胡注射液ADR/AE病例存在不当使用,如大剂量使用(5例)、静脉给药(6例)、违反配伍禁忌(7例)。重、轻型病例中,ADR、AE之比分别为1.7:1和1.1:1;肯定有关、很可能有关、可能有关3个关联程度等级,重、轻型病例中3个等级病例数之比依次为25:14:5和44:9:16。结论:目前低强度的证据表明柴胡注射液ADR/AE病例中不当使用情况严重,部分柴胡注射液的适应人群有待进一步的研究,如老人和儿童。应加强对各级医务人员规范使用柴胡注射液的教育,鼓励和支持各级医护人员如实上报ADR/AE的同时规范发表ADR/AE。

Background： Chaihu Injection （CI）, which is widely used in treatment of febrile diseases, is an aqueous solution of Chaihu （Radix Bupleuri Chinensis） or Nanchaihu （Radix Bupleuri Scorzonerifolii） prepared by steam distillation. Objective： This study aims at finding out the possible causes for adverse drug reaction or adverse event （ADR/AE） caused by CI and assessing its safety based on existing evidence. Search strategy： Manual search was not conducted. Electronic search was conducted by two authors in China National Knowledge Internet （CNKI） database and Chongqing VlP database （VlP）. The search ended in June 30th, 2009. Inclusion criteria： Studies of ADR/AE induced by Cl were collected comprehensively without considering language of literature and outcome indicators. Search results were not limited by patient＇s age, gender,race, primary disease, etc. herbal medicine decoction or Data extraction and analysis： nterventions were using C other drugs containing Chaihu Two authors conducted data was used to develop data extraction forms. Because of analysis was conducted. alone or CI combined with other drugs （Chinese were excluded）. extraction independently. Microsoft Excel software heterogeneity of the studies, only a descriptive Results： Totally 83 studies with 203 cases were included in this review. Without the yield data and total amount of using, we cannot tell the incidence of ADR/AE induced by CI as well as assess the risk and safety of Cl. The constituent ratio of severe cases was higher in children and old people than in other age groups. For most intramuscular cases, ADR/AE happened in 30 rain after injection （constituent ratio of cumulative incidence in 30 min was 93.8%）; for intravenously guttae patients, 4 cases of ADR/AE happened in the process of infusion; for first users, constituent ratio of cumulative incidence in 30 min and constituent ratio of cumulative incidence of severe cases in 30 min were higher than cases who had used Cl before. Most ADRs/ AEs were caused by incorrect use of Cl, such as excessive doses （5 cases）, intravenously guttae administration （6 cases）, and violating incompatibility rules （7 cases）. The incidence ratios of ADR and AE for severe and mild cases were 1.7 ： 1 and 1.1 ： 1, respectively; the ratios of the three relevant levels described as definitely related, most probably related and possibly related in the two types （severe and mild） of cases were 25 ： 14 ： 5 and 4=4 ： 9 ： 16, respectively. Conclusion： Present evidence with low level shows that incorrect use is the main cause of ADR/AE of Cl. Whether Cl is proper for children and old people still needs further research. Training for correct use of Cl is necessary for medical workers. Much improvement in reporting ADR/AE based on ＂Recommendations for Reporting Adverse Drug Reactions and Adverse Events of Traditional Chinese Medicine＂ is in need.