基于真实世界使用榄香烯乳状注射液影响肝功能的倾向性评分分析

doi:10.19803/j.1672-8629.20211116

摘要/Abstract

摘要： 目的探索真实世界中使用榄香烯乳状注射液的人群导致肝功能损伤的影响因素。方法在中国中医科学院中医临床基础医学研究所建立的大型医院信息系统（HIS）集成数据仓库中,收集全国21家三甲医院在2003年1月1日至2019年7月31日期间使用过至少1次榄香烯乳状注射液的患者共4 421人,提取导致肝功能异常患者27例,通过SOMTE抽样处理,最终得到肝功能损伤组27例,对照组108例。将135例中所有影响肝功能异常因素通过Logistic回归,不带协变量的梯度提升机倾向评分加权Logistic回归以及带协变量的梯度提升机倾向评分加权Logistic回归进行处理,分析影响肝功能损伤的因素。结果 Logistic回归显示P<0.05有4个因素,即多系统继发恶性肿瘤,用药前7 d合并用药呋塞米、利多卡因（赛罗卡因）、维生素类,进一步运用倾向评分方法进行分析;结果显示多系统继发性恶性肿瘤对肝功能有影响,使用榄香烯乳状注射液前7 d内服用呋塞米对肝功能可能有影响,使用榄香烯乳状注射液期间的合并用药利多卡因是否会导致肝功能损伤还需进一步研究,使用榄香烯乳状注射液期间的合并用药维生素类不会影响肝功能。结论未有直接的证据证明使用榄香烯乳状注射液会导致肝功能损伤,如需直接证明,还需要严格的随机对照实验验证。

关键词: 榄香烯乳状注射液, 倾向性评分, 肝功能损伤, 真实世界

Abstract: Objective To explore the causes of liver function injury associated with elemene emulsion injection in the real world. Methods The clinical data on 4 421 patients who had used elemene emulsion injection at least once in 21 big hospitals nationwide between January 1, 2003 and July 31, 2019 were collected from the integrated data warehouse of the large hospital information system (HIS) established by the Institute of Clinical Basic Medicine of Chinese Medicine of the Chinese Academy of Traditional Chinese Medicine. Twenty-seven patients with abnormal liver function were included. Through SOMTE sampling, 27 patients with liver function impairment and 108 patients in the control group were finally obtained. All the factors that affected normal liver function in the 135 cases were processed by Logistic regression, weighted Logistic regression of gradient elevator tendency scores without covariates and weighted Logistic regression of gradient elevator tendency scores with covariates. Results Logistic regression showed that there were 4 factors (P<0.05), namely, multiple secondary malignant tumors, combination with furosemide 7 days before administration, combined use with lidocaine (sirocarine), and vitamins. Further analysis using the tendency score method showed that multiple secondary malignant tumors had an impact on liver function. The use of furosemide 7 days before elemene emulsion injection might affect liver function. Whether lidocaine combined with elemene emulsion injection would lead to liver function injury needs to be studied, and vitamins combined with elemene emulsion injection would not affect liver function. Conclusion There is no compelling evidence that the use of elemene emulsion injection will lead to liver function injury. For more evidence, rigorous randomized controlled experiments are required.

Key words: elemene emulsion injection, propensity score, liver function injury, the real world

中图分类号:

R927.1

杜莹, 赵晓晓, 谢雁鸣, 余小康. 基于真实世界使用榄香烯乳状注射液影响肝功能的倾向性评分分析[J]. 中国药物警戒, 2023, 20(2): 191-195.

DU Ying, ZHAO Xiaoxiao, XIE Yanming, YU Xiaokang. Effects of elemene emulsion injection on liver function injury in the real world based on propensity scores[J]. Chinese Journal of Pharmacovigilance, 2023, 20(2): 191-195.

参考文献

[1] ZHANG Y, JIA YJ, LI XJ, et al.Clinical observation on the treatment of moderate malignant pleural effusion treated by elemene injection combined heat[J]. Tianjin Journal of Traditional Chinese Medicine(天津中医药), 2018, 35(5): 340-343.
[2] HOU W, LIN HS.Clinical study of elemene injection combined with radiotherapy in the treatment for non-small cell lung cancer patient with brain metastasis[J]. China Cancer(中国肿瘤), 2007, 16(12): 1021-1022.
[3] YANG M, TAN Y, LI G, et al.Clinical observation of elemene injection combined with radiotherapy on breast cancer with brain metastasis[J]. Guide of China Medicine(中国医药指南), 2018, 16(20): 9-10.
[4] ZHOU XQ, JI B, QIU XJ, et al.Clinical observation of elemene injection combined with radiotherapy on lung cancer with brain metastasis[J]. Chinese Clinical Oncology(临床肿瘤学杂志), 2010, 15(11): 1014-1016.
[5] ZHAO YS, ZHAO X.Clinical observation of elemene emulsion injection, NP regimen and thalidomide in the treatment of advanced non-small cell lung cancer[J]. China’s Naturopathy(中国民间疗法), 2021, 29(3): 104-106.
[6] ROSENBAUM PR, RUBIN DB.The central role of the propensity score in observational studies for causal effects[J]. Biometrika, 1983, 70(1): 41-55.
[7] ROSENBAUM PR, RUBIN DB.Constructing a control group using multivariate matched sampling methods that incorporate the propensity score[J]. The American Statistician, 2012, 39(1): 33-38.
[8] YE XQ, XIE YM, WANG LN, et al.Application of propensity score method in therapeutic evaluation of non-randomized data produced by TCM complex intervention[J]. China Journal of Traditional Chinese Medicine and Pharmacy(中华中医药杂志), 2015, 30(10): 3414-3417.
[9] ZHUANG Y, XIE BT, WENG SX, et al.Construction and realization of real world integrated data warehouse from HIS on re-evaluation of post-marketing traditional Chinese medicine[J]. China Journal of Chinese Materia Medica(中国中药杂志) , 2011, 36(20): 2883-2887.
[10] MI SH, LI HF, GUO YH.A case of abnormal liver function caused by elemene[J]. Chinese Journal of New Drugs(中国新药杂志), 2000, 9(5): 345.
[11] LIU XN, SHEN MH, LIU XS.Analysis of influencing factors of abnormal liver function in postoperative patients with gynecological malignant tumors[J]. Progress in Obstetrics and Gynecology(现代妇产科进展), 2019, 28(9): 701-703.
[12] SONG YQ, LIU ZM, WANG C.Analysis the etiological factor of hepatic dysfunction of patients with tumor[J]. Journal of Clinical Hepatology(临床肝胆病杂志), 2003 (4): 248-249.
[13] CHEN QW, ZHENG XQ, CHANG CY, et al.Clinical features of abnormal liver function in cancer patients with chemotherapy and its related risk factors[J]. Zhejiang Medical Journal(浙江医学), 2017, 39(12): 976-978, 1001.
[14] CHEN FC, LI KJ, LIU P.Incompatibility and adverse reactions of furosemide[J]. Chinese Journal of Misdiagnostics(中国误诊学杂志), 2006, 6(14): 2847-2848.
[15] GUO TJ, LIN MA.Rare adverse reactions of furosemide[J]. Adverse Drug Reactions Journal(药物不良反应杂志), 2002, 4(3): 163-166.
[16] MASUI. After repeated epidural lidocaine blocking treatment for herpes zoster, the patient developed unknown fever and abnormal liver function[J]. Foreign Medicine. Virology volume(国外医学病毒学分册), 1995(3): 94-95.
[17] CHEN RB, GAI GZ, XIE YM, et al.Analysis of the effect of Maixuekang capsule on the treatment outcome of ischemic cerebrovascular disease by propensity scoring method[J]. World Chinese Medicine(世界中医药), 2019,14(1): 104-108.
[18] AI QH, XIE YM, LI L, et al.Effects of Shenqifuzheng injection on ALT lever using propensity score[J]. China Journal of Traditional Chinese Medicine and Pharmacy(中华中医药杂志), 2014, 29(5): 1687-1691.
[19] LI YX, YANG W, XIE YM, et al.Effect of Dengzhan Xixin injection on ALT and AST evaluated by propensity scoring: an analysis of 1641 cases[J]. Traditional Chinese Drug Research and Clinical Pharmacology(中药新药与临床药理), 2015, 26(3): 401-405.
[20] ZHANG Y, YANG W, JIANG JJ, et al.Impact analysis of the clinical use of Shenfu injection on liver function by using propensity score methods[J]. Journal of Liaoning University of Traditional Chinese Medicine(辽宁中医药大学学报), 2016, 18(9): 66-70.
[21] YANG W, XIE YM, ZHUANG Y.Explore method about post-marketing safety re-evaluation of Chinese patent medicines based on HIS database in real world[J]. Chinese Journal of Traditional Chinese Medicine(中国中药杂志), 2011, 36(20): 2779-2782.