Analysis of Risk Factors for Toxic Serum Digoxin Concentrations in Taiwan Patients: A Nested Case-Control Study

臺灣人Digoxin毒性血中濃度之危險因子分析：巢式病例對照研究

姜采玲(Tsai-Ling Chiang) ； 高啟蘭(Chi-Lan Kao) ； 柯文欽(Wen-Chin Ko) ； 吳庭青(Ting-Ching Wu) ； 黃婉翠(Wan-Tsui Huang)

《臺灣臨床藥學雜誌》 28卷4期 (2020/10) Pp. 306-319

https://doi.org/10.6168/FJCP.202010_28(4).0006

摘要

Objective: Digoxin has a narrow therapeutic range and toxic serum concentration of ＞ 2 ng/mL; hence, its safe usage is crucial in clinical practice. Despite pharmacokinetic studies demonstrating several factors affecting serum digoxin concentrations (SDCs), the factors' clinical significance has not been fully assessed in observational studies. Methods: This retrospective cohort study with a nested case-control analysis used medical records from a medical center in Taiwan between October 2011 and September 2016. We included patients with SDCs reports. Patients with and without reports of toxic SDCs were defined as cases and controls, respectively. Case-control matching was performed using age and sex. Conditional logistic regression analysis was used to determine risk factors for toxic SDCs. Results: We identified 61 cases (median age: 82.0 years) and 239 controls (median age: 82.0 years). The cases had a higher proportion of patients taking digoxin dose ＞ 0.125 mg/day (32.8% vs. 10.9%, p ＜ 0.001) and serum creatinine levels (1.6 vs. 1.0 mg/dL, p ＜ 0.001) than did the controls. Risk factors for toxic SDCs included a daily digoxin dose of ＞ 0.125 mg and chronic kidney disease (CKD) stages III and IV/V (non dialysis) (adjusted odds ratio: 12.21, 2.89, and 8.67, respectively). Conclusions: This is the first observational study, which included controls for analysis, to determine clinically significant risk factors for toxic SDCs. Clinically significant risk factors for toxic SDCs in the elderly patients are a daily digoxin dose of ＞ 0.125 mg and CKD stages III-V.

關鍵字

Toxic Serum Digoxin Concentrations ； Nested Case-Control Study ； Taiwan ； Digoxin Dose ； Chronic Kidney Disease

並列摘要

目的：Digoxin屬於治療範圍狹窄（毒性血中濃度 ＞ 2 ng/mL）的藥物，其用藥安全在臨床上是很重要的。雖然藥物動力學研究顯示多種因子會影響digoxin血中濃度，但這些因子的臨床顯著性還未在觀察性研究中被完整地評估。方法：本篇是運用巢式病例對照分析的回溯性世代研究，研究材料來自臺灣某醫學中心於2011年10月～2016年9月的電子病歷。納入具有digoxin血中濃度報告的病人，將具有毒性血中濃度者歸類至病例組；不具有毒性血中濃度者，以年齡和性別和病例配對後歸類至對照組。以條件式邏輯斯迴歸分析digoxin毒性血中濃度的危險因子。結果：病例組共有61人，對照組共有239人，兩組的年齡中位數皆為82.0歲。相對於對照組，病例組有較多病人服用每日digoxin劑量 ＞ 0.125 mg（32.8% vs. 10.9%, p ＜ 0.001）。病例組的肌酸酐（serum creatinine）中位數較對照組為高（1. vs. 1.0 mg/Dl , p ＜ 0.001）。Digoxin毒性血中濃度的危險因子包含：每日digoxin劑量 ＞ 0.125 mg、第三期慢性腎臟病、第四或第五期慢性腎臟病（不含透析）（校正後勝算比[adjusted odds ratio]分別為12.21、2.89及8.67）。結論：這是第一篇觀察性研究，以巢式病例對照分析digoxin毒性血中濃度的臨床顯著危險因子。研究發現其臨床顯著危險因子包含：每日digoxin劑量 ＞ 0.125 mg及第三到第五期的慢性腎臟病，特別是在年老的病人。

並列關鍵字

Digoxin毒性血中濃度 ； 巢式病例對照研究 ； 臺灣 ； Digoxin劑量 ； 慢性腎臟病