請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/19872
標題: | 某醫學中心Amiodarone相關肝傷害監測之探討 Guideline Concordance of Monitoring Amiodarone-associated Liver Injury at a Medical Center |
作者: | Yi-Ting Tsou 鄒依庭 |
指導教授: | 何?芳 |
關鍵字: | Amiodarone,肝功能監測,台灣,藥物引致肝傷害, amiodarone,guideline concordance,drug-induced liver injury,Taiwan., |
出版年 : | 2015 |
學位: | 碩士 |
摘要: | 研究背景 Amiodarone為效用廣且臨床常用之抗心律不整藥物,但可能引起肝、肺、眼、甲狀腺等多種器官系統不良反應,其中,amiodarone相關的肝傷害雖不乏嚴重肝毒性案例報導,卻常被輕忽。關於amiodarone藥物治療之文獻多建議監測各項可能副作用之用藥前檢驗基礎值並於後續定期追蹤,然而,國內鮮少有關於amiodarone安全監測及相關肝傷害(drug-induced liver injury; DILI)風險因子的研究。 研究目的 探討臨床對於新使用及長期使用amiodarone病人之遵照指引建議監測肝臟與甲狀腺相關副作用的比率與amiodarone相關肝傷害之發生情形。 研究材料與方法 本研究採回溯性分析,以某醫學中心2010年8月1日至2012年9月30日之醫療資訊為研究材料,研究對象年齡大於18歲且(1)新使用amiodarone(含口服與注射劑型)之病人,亦即於納入研究前至少六個月期間無amiodarone處方;(2)長期使用amiodarone之病人,即新使用者且amiodarone處方至少持續180天以上。所彙整之資料包括研究對象基本資料、疾病史、肝功能與甲狀腺功能檢驗值以及藥品處方,並以alanine aminotransferase(ALT)上升達3倍正常值上限定義為肝傷害事件。本研究以敘述性統計描述新使用者和長期用藥者的肝功能(ALT)與甲狀腺功能(thyroid-stimulating hormone; TSH)之用藥前基礎值監測以及用藥後180天內之監測情形,並以回歸分析探討遵循肝功能監測指引之影響因子。 研究結果 研究期間amiodarone處方總計70,512筆(8,984人),其中符合定義之新使用者共5,487位,符合長期用藥定義者計309人(5.6%)。新使用者之ALT、TSH用藥前基礎值監測率分別為82.1%、29.0%;長期用藥群ALT、TSH之基礎值監測率76.7%、24.3%,另兩群體同時監測ALT及TSH基礎值分別為 26.4%、21.0%;長期用藥群開始用藥六個月期間監測ALT、TSH比率分別為69.6%、31.7%,同時監測ALT及TSH者佔23.6%。 長期用藥群中遵循指引建議在用藥前及用藥後六個月期間監測ALT 共180位(58.3%),影響遵循監測建議的因子為具肝病史(odds ratio [OR], 6.08; 95%CI, 1.84-24.64)、高脂血症(OR, 2.86; 95%CI, 1.31-6.48)及共病症數目較多(OR, 95%CI; 1.06-1.19)、用藥180天期間併用可能引致肝傷害的藥物(OR, 2.14; 95%CI, 1.16-4.21)、住院次數較多(OR, 1.45; 95%CI, 1.02-2.11)、首次開方單位為加護病房者(OR, 5.78; 95%CI, 1.67-27.37)與首次開方單位為門診(OR, 0.20; 95%CI, 0.1-0.38)。 長期用藥群中有17人(6.3%)發生肝傷害事件,與先前研究之比率相近;發生肝傷害者(n=17)與未發生者(n=292)兩組之病人基本特性無明顯差異。在新使用amiodarone且具 ALT 基礎值監測之病人中(n=3721),發生肝傷害事件計564人(15.2%),而其中具肝病史者(n=397)與無肝病史者(n=3324)兩組之肝傷害發生比率無顯著差異。 結論 總體來說,amiodarone使用者肝功能監測率(含基礎值、用藥期間監測)與國外研究相似,用藥期間監測率稍低於基礎值監測率,而有關甲狀腺功能之監測比例卻不盡理想。本研究提供臨床醫療人員了解目前amiodarone使用者肝功能與甲狀腺監測情形以及amiodarone相關肝傷害之比率,應有助於評估amiodarone不良反應相關性與及早偵測藥物不良反應的發生,期增進藥物治療的安全性與有效性。 Background Amiodarone is an effective and widely used anti-arrhythmic agent; however, it is associated with multi-organ adverse effects. Hepatic adverse effects of amiodarone are often neglected in clinical practice even though severe ones have been reported. Consensus guidelines often recommend that liver and thyroid function tests should be conducted before amiodarone therapy and semiannually thereafter. Little is known about the guideline concordance of laboratory monitoring and risk factors associated with amiodarone hepatotoxicity in Taiwan. Objective The study aimed to determine the proportion of and predictors for patients receiving liver and thyroid monitoring at baseline and within 180 days of initiation of chronic amiodarone therapy and the incidence of amiodarone-associated liver injury. Materials and Methods This is a retrospective study using hospital electronic medical records to identify new amiodarone users (age >18 years) who had a 180-day washout period before the index date at a medical center from August, 2010 to September 30, 2012. Patients with continuous amiodarone dispensing records ≥ 180 days were defined as chronic users. Data on patient demographics, comorbidity, liver and thyroid function tests, and concomitant medications were collected. The monitoring rate at baseline and within 6 months of amiodarone initiation, and the incidence of amiodarone-associated liver injury, defined as the first occurrence of alanine aminotransferase (ALT) higher than 3 times of upper limit of normal after amiodarone initiation, were determined. Logistic regressions were also used to explore factors associated with the guideline concordance of laboratory monitoring for assessing amiodarone hepatotoxicity. Results A total of 5,487 new amiodarone users were identified from 70,512 prescriptions during the study period. Eligible patients to be included for further analyses were 309 (5.6%) and 4,235 (77.2%) for chronic amiodarone users and liver injury cohorts (with baseline and follow-up ALT levels). Among the new users, baseline monitoring rates of ALT, TSH, or both were 82.1%, 29.0%, and 26.4%, respectively. As for the cohort of chronic users, the monitoring rates of ALT, TSH, or both at baseline were 76.7%, 24.3%, and 21.0%; and those for within first 6 months of amiodarone therapy were 69.6%, 31.7%, and 23.6%. There were 180 (58.3%) patients with ALT monitored at baseline and within 180 days of amiodarone initiation. Predictors associated with concordance of ALT monitoring included comorbid liver diseases (odds ratio [OR] 6.08, 95%CI 1.84-24.64), hyperlipidemia (OR 2.86, 95%CI 1.31-6.48), number of comorbidities (OR 1.12, 95%CI 1.06-1.19), concomitant drugs of liver injury potential (OR 2.14, 95%CI 1.16-4.21), number of hospitalization (OR 1.45, 95%CI 1.02-2.11), amiodarone initiated at ICU settings (OR 5.78, 95%CI 1.67-27.37); yet, amiodarone initiated at outpatient settings (OR, 0.20; 95%CI, 0.1-0.38) was negatively associated. Liver injury episodes occurred in 17 (6.3%) and 564 (15.2%) patients for cohorts of chronic users (n=309) and new users with baseline ALT (n=3721), respectively. Conclusions In general, monitoring rates for liver functions at baseline, within 180 days of amiodarone initiation, and the incidence of liver injury in the chronic users were compatible with earlier studies, but monitoring rates for thyroid functions were less than ideal. Even though predictors for monitoring potential liver toxicity were identified, risk factors for amiodarone-associated liver injury await further delineation. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/19872 |
全文授權: | 未授權 |
顯示於系所單位: | 臨床藥學研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-104-1.pdf 目前未授權公開取用 | 1.74 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。