血液透析患者萬古黴素的給藥方式

研究背景：慢性腎病變(chronic renal disease)是腎臟功能逐漸喪失的一種疾病，也是台灣最嚴重的疾病之一，2 0 0 7年共有高達5萬名慢性腎衰竭(chronic renal failure)病患必須接受定期透析治療(dialysis)。腎臟衰竭的患者接受血液透析治療會增加感染的危險性已被文獻證實和廣為討論。Vancomycin經常被用來治療具抗藥性的革蘭氏陽性菌感染上，現今的給藥方式是每4到7天在透析後靜脈輸注 1 gm vancomycin，也有學者研究在透析過程的最後一個小時給予vancomycin 500mg，可以維持5-20 mcg/mL的藥物濃度，並且可以讓患者不用在醫療院所多停留一個小時，目前台灣未有透析過程給藥的研究，本試驗希望能提供一便利患者並且具有足夠藥物濃度的給藥方式。研究目的：Vancomycin可提供有效而且方便的治療感染具抗藥性的革蘭氏陽性菌的血液透析患者，門診的患者不需要住院就可以良好的治療與控制，目前台灣大部分醫療院所採用的給藥方式為透析後給藥，此方法病患在透析後必須再輸注一小時的藥物，造成病患不便也會增加醫療支出；所以國外學者研究在透析過程給藥的方式，在國內的醫師經訪查後也有採用，此研究的目的是希望在給予起始劑量vancomycin 1gm之後，每次透析結束前一個小時輸注vancomycin 500mg，能縮短血液透析患者停留在醫院的時間和給予醫療人員便利，並監測藥物的濃度是否足夠。研究方法：本研究為前瞻性觀察研究(prospective observational study)，研究期間民國97年5月21日起，至民國98年5月20日止，研究中山醫學大學附設醫院需要長期血液透析成人患者，因感染症經主治醫師判定需使用vancomycin治療的患者。17位病患起始劑量為vancomycin 1 gm靜脈點滴輸注一個小時，經簽署受試者同意書後，開始監測透析前vancomycin血中濃度，及透析結束前一小時監測vancomycin血中濃度，接著輸注維持劑量vancomycin 500mg一個小時，與透析一起結束。結果：17位病患，總共獲得102個藥物濃度，全部透析前濃度(mcg/mL)介於5~20有49 (96.1%)個濃度，大於20有2 (3.9%)個濃度，最低濃度為7.22，最高為22.75，沒有低於5的濃度；全部血液透析前濃度的平均值為12.6±3.6；沒有殘餘腎功能的患者(n=10)平均的血中濃度為14.2±3.6 mcg/mL。透析過程最低血中濃度(mcg/mL)小於5有1 (2.0%)個濃度，其餘濃度都介於5~20，沒有大於20的濃度。血液透析3小時，vancomycin給藥前平均濃度(mcg/mL)為9.26±2.8。 共變數分析顯示藥物劑量與濃度呈現正相關，有殘餘腎功能患者與藥物濃度顯示負相關，因此體重和還有尿液的患者都會影響藥物濃度。結論與建議：患者使用Vancomycin起始劑量1 gm之後，每次血液透析過程最後一個小時給予維持劑量 500mg，可以有足夠劑量和節省病患的時間，並提供醫護人員方便的給藥方式。建議每週監測藥物濃度，特別是還有殘餘腎功能或過重的病患，才能適時給予補充劑量。

Background Chronic kidney disease (CKD), also known as chronic renal disease, is a progressive loss of renal function. In the year 2007, approximately 50,000 patients in the end stage of renal disease (ESRD) were maintained on chronic dialysis in Taiwan. The risk of infection in hemodialysis patients will increase as confirmed by literature and discussions. Vancomycin is primarily active against gram-positive bacteria, and the current administration is intravenous vancomycin 1 gm after dialysis at every 4-7 days. Some investigators have recommended the convenient practice of administering vancomycin doses during the last hour of the hemodialysis treatment, and will reduce patient’s time staying in hospital. The method has not been researched in Taiwan, but we hopes to provide a convenient drug dosing regimen that maintains adequate predialysis plasma concentrations.Methods From 21st May 2008 to 20th May 2009, adult patients who received regular hemodialysis in Chung Shan Medical University Hospital and were treated with vancomycin were prospectively enrolled. All patients were administered with a vancomycin loading dose of 1 gm IV after dialysis, and maintenance doses of 500 mg IV during the last hour of all dialysis sessions. Vancomycin levels were determined predialysis for all the subsequent hemodialysis sessions and before maintenance doses. Clinical Laboratory data and drug concentrations were recorded.Result For the 17 patients and 102 serum concentrations studied, the predialysis concentration range of 5 to 20(mcg/mL) were achieved for 49 levels (96.1%). There were no concentrations less than 5 mcg/mL; Average concentration of all pre-hemodialysis was 12.6 ± 3.6 mcg/mL. Average concentration of all pre-hemodialysis for anuric patients (n=10) was 14.2±3.6 mcg/mL. There were 51 levels (98%) ranging from 5 to 20 mcg/mL before maintenance doses, except 1 level (2.0%) below 5 mcg/mL. The average concentration was 9.26±2.8 mcg/mL. Dosage and concentrations were related positively and residual renal function and drug concentrations showed a negative correlation by Analysis of covariance (ANCOVA). Therefore, dosage and residual renal functions affected vancomycin concentration in hemodialysis patients。ConclusionOur results indicate that a loading dose of vancomycin 1 gm IV and then an intradialytic dose of vancomycin 500 mg IV conveniently maintain adequate predialysis plasma concentrations. Suggesting the monitoring of vancomycin levels once a week, especially of those patients who are overweight or have residual renal function it may be determined if a supplemental dose is needed.