台灣某醫學中心血液透析病人使用 Vancomycin 的藥物療效濃度監測
The Therapeutic Drug Monitoring of Vancomycin for the Patients with Hemodialysis in a Medical Center in Taiwan
中文摘要
萬古黴素(vancomycin)屬於醣肽類(glycopeptides)抗革蘭氏陽性菌的抗生素，常用 於治療抗藥性金黃色葡萄球菌(Methicillin-Resistant Staphylococcus aureus；MRSA) 或是病人對青黴素類抗生素產生過敏反應之替代藥物。其主要排除途徑為腎絲球 過濾排除，常見的嚴重副作用為腎毒性與耳毒性，而在腎臟功能不全的病人族群 更容易增加毒性副作用發生的機率，因此，在腎臟功能不全的病人更需嚴密監測 萬古黴素的血中濃度。針對血液透析的病人，臨床醫療人員大多需要依賴密集地 藥物療效監測或個人經驗來給予藥物劑量；文獻指出，高效率/高通透性血液透 析(high-efficiency/high-flux hemodialysis)會清除血液中萬古黴素的藥物濃度，所 以，血液透析可能會影響藥物治療的效果。
本研究為前瞻性的連續性個案報告，希望能了解萬古黴素在接受血液透析病人族 群的藥物動力學變化，整理並分析出適合醫院中血液透析病人的萬古黴素治療劑 量與療程，以增進病人的用藥安全。研究期間自 2007 年 1 月 1 日起至 2008 年 6 月 30 日止，進行前已獲執行醫院之人體試驗審議委員會同意。研究對象以接受 血液透析之慢性腎臟衰竭病人，合併發生確定或疑似感染症，經醫師處方萬古黴 素用來治療感染症者，且經簽署同意書後為收案個案。建議處方劑量為每公斤體 重給予靜脈注射萬古黴素 15 毫克，在藥物輸注結束後 1 小時(S1)、接受下次血 液透析前(S2)與結束透析後 3 小時(S3)各需抽血監測藥物濃度；同時記錄個案相 關臨床數據。
研究期間為 18 個月；共收集 27 位使用萬古黴素之血液透析病人，其中有 15 位 病人因無法完成簽署病人同意書、抽血時間點不符合而被排除，共有 12 位病人 完成試驗，其中 66.67%為男性，平均年齡為 64.18±11.63 歲，透析前體重為 59.15
±16.67 公斤，透析後體重為 57.24±16.30 公斤，殘餘腎功能為 11.34±4.63 mL/min，
只有 16.67%的病人接受高通透性的透析方式。使用萬古黴素的劑量為 791.67±
199.83 毫克，依體重換算為 13.97±3.70 mg/kg。S1 與 S3 的濃度分別為 23.94±
12.34、10.09±5.81 mcg/mL，平均接受血液透析的時間為 3.85 小時，透析期間移 除約 19.19±9.62%的萬古黴素血中濃度；非血液透析與透析期間的萬古黴素清除 率及排除速率常數(k)分別為 9.91±7.37 與 18.27±14.74 mL/min、0.02±0.02 與 0.04
±0.02 hour-1。
因研究設計的限制，無法進一步確認透析後萬古黴素維持劑量的合理性，但多數 使用人工血管的透析病人因管路流速的限制可能需使用非高通透性的透析方 式，而且使用人工血管透析的血液感染率高於其他種類的透析方式。從本研究中 發現，萬古黴素的起始劑量為每公斤體重 15 毫克時，可能無法符合血液透析病
人發生嚴重血液感染的臨床需求，而非高通透性的血液透析方式仍會將血液中的 萬古黴素移除，如果透析後的濃度需要維持在 20 mcg/mL，可考慮每次透析結束 後再給予萬古黴素藥物約 250-300mg，應可以符合臨床上的需求。
英文摘要
Vancomycin, a glycopeptide antibiotic agent for methicillin-resistant Staphylococcus aureus (MRSA) infection, is mainly eliminated by glomerular filtration of kidney. The clearance of vancomycin decreases substantially in patients with renal dysfunction or anuria. Patients with high serum vancomycin concentrations or renal function
impairment are at risk of developing vancomycin-induced nephrotoxicity or
ototoxicity. Many clinicians would adjust the dose of vancomycin by the individual experience or monitoring its serum level frequently when uses it on hemodialysis patients. But some studies have recommended that significant amounts of vancomycin are easily removed in the type of high-flux or high-efficient hemodialysis. The
possibility to cause adverse effects could be low, but the incidence of treatment failure is then high. The best and convenient practice of administering vancomycin in
hemodialysis patients is still controversial.
Objective
The current study is to determine the pharmacokinetic parameters of vancomycin in patients with hemodialysis. We hope to find the optimal vacomycin regimen for the population in hospital.
Material and Method
Patients received hemodialysis between January 2007 and June 2008 would be invited to join the trial. Written informed consent was signed by each subject prior to
participation in the trial according to the research protocol approved by Institutional Review Board (IRB). They had been included in the study if they must be treated with vancomycin due to any infected disease. The recommended dose of vancomycin was 15 milligram per kilogram at a time. The first vancomycin serum concentration (S1) should be drawn after completion of vancomycin infusion, the second one (S2) immediately before starting the next hemodialysis, and third one (S3) should be drawn at 3 hours after the hemodialysis is completed. The three serum levels would be recorded and analyzed to yield pharmacokinetic parameters.
Results
There were 12 patients-time samples of vancomycin serum concentration data. Only one-sixth of patients were received high-flux or high-efficient hemodialysis. The average dose of vancomycin was 13.97±3.70 mg/kg. The pharmacokinetic parameters (mean±SD) were found that S1 was 23.94±12.34 mcg/mL and S3 was 10.09±5.81 mcg/mL. The pre-hemodialysis clearance and elimination constant (k) of vancomycin
was 9.91±7.37 mL/min and 0.02±0.02 hour-1, 18.27±14.74 mL/min and 0.04±0.02 hour-1 in intra-hemodialysis. Amount of 19.19±9.62 % vancomycin concentrations were removed during almost 4-hours dialytic session.
Conclusion
The usual kind of hemodialysis via venous catheters was not high-flux/high-efficient dialysis. And central venous catheter vascular access, whether cuffed or uncuffed, has a much higher infection risk. We found that vancomycin had been removed around one-fifth by non-high-flux/high-efficient hemodialysis. Based on the results, an initial dose of vancomycin 15 mg/kg may be not adequate to get target levele of 15-20 mcg/mL for patients with complicated infection. The dose of vancomycin 250-300 mg after every subsequent non-high-flux/high-efficient hemodialysis is recommended.
