三七总皂苷注射剂所致肝功能损伤的主动监测研究

Active monitoring of liver injury related to Panax notoginseng saponines injection

目的:探究三七总皂苷注射剂所致肝功能损伤在真实世界的发生率、临床特点及相关危险因素,为临床安全使用提供参考。方法:通过中国医院药物警戒系统搜索2021年1月1日至2022年3月21日在长沙市第一医院接受三七总皂苷注射剂治疗的患者,采用巢式病例对照研究方法从该人群中选择病例组与对照组。病例组为中国医院药物警戒系统中触发警报信号指示肝功能异常,经药师判定为药品不良反应的人群;在未触发警报信号的患者中,以年龄上下浮动5岁和性别相同与病例组按1∶4进行匹配,得到对照组。分析肝功能损伤的发生情况,采用配对Logistic回归进行影响因素分析。结果:三七总皂苷注射剂所致肝功能损伤的发生率为0.46%,属“偶见”不良反应;93%发生在用药后5~10 d,以轻至中度转氨酶升高为主要表现。单因素Logistic回归分析显示无适应证、溶媒类型(生理盐水)、用药时间>7 d、合并手术、吸烟、饮酒、合用质子泵抑制剂、合用低分子肝素与三七总皂苷注射剂导致肝功能损伤相关(P<0.05)。多因素Logistic回归分析显示溶媒类型(生理盐水)、合并手术是具有统计学意义的独立危险因素(P<0.05)。结论:利用中国医院药物警戒系统开展不良反应主动监测,反映真实世界三七总皂苷注射剂所致肝功能损伤的发生情况,为提高用药安全性提供科学可靠的参考,也为药物安全性评价提供了新的研究方法。

OBJECTIVE To explore the incidence, clinical characteristics and related risk factors of liver injury related to Panax notoginseng saponines(PNS)injection in real world,so as to provide reference for clinical safe use.METHODS From January 1,2021 to March 21,2022,patients who received PNS injection in our hospital were searched through the China Hospital Pharmacovigilance System(CHPS).Then, we used a nested case-control study method to select experimental and control groups from this population.The experimental group was a group of people with adverse drug reactions determined by pharmacists after that the alarm signal was triggered in CHPS.The control group was matched 1:4 with the experimental group by age±5 years and the same gender, and randomly selected from the remaining not triggered patients.Univariate and multivariate Logistic regressions were carried out to analyze the risk factors of liver injury.RESULTS The incidence of liver injury caused by PNS injection was 0.46%,which was an “occasional” adverse reaction.There were 93% of liver injury that occurred within 5~10 days after treatment, with mild to moderate elevation of transaminase as the main manifestation.Univariate Logistic regression analysis showed that no indication, vehicle type(normal saline),medication days>7 days, combined surgery, smoking, drinking, combined use of proton pump inhibitors, combined use of low molecular weight heparin were related to liver injury caused by PNS injection(P<0.05).Multivariate Logistic regression analysis showed that the type of vehicle(normal saline) and combined surgery were statistically significant independent risk factors(P<0.05).CONCLUSION To carry out active monitoring research, CHPS is used to reflect the occurrence of liver injury caused by PNS injection in the real world, providing a scientific and reliable reference for improving drug safety and a new research method for drug safety evaluation.