環利尿劑與加護病房中常用靜脈注射藥之物理不相容性研究

Physical Incompatibilities of Loop Diuretics with Intravenous Medications Frequently Used in Intensive Care Units

邵偉城(Wei-Cheng Shao)

指導教授 ： 林慧玲

國立臺灣大學/醫學院/臨床藥學研究所/碩士(2012年)

https://doi.org/10.6342/NTU.2012.03357

摘要

研究背景
醫藥錯誤（medication error）是造成治療效果變差、失敗或是對病人造成傷害甚至死亡的重要原因，藥品注射劑型又比口服劑型更容易造成醫藥錯誤。給與注射劑藥品時發生的醫藥錯誤型態中，潛在藥品物化性質不相容（incompatible）的機率可高達25%，且造成的傷害多為中至重度甚至危及生命（life-threatening）。分析臺大醫院13個加護病房的電子醫令開方檔，排名前10名的不相容靜脈注射藥品組合中，有4項包含了furosemide，文獻回顧其Y-site相容性發現，furosemide或其他藥品的濃度與臺灣臨床使用不同，許多文獻的相容性資料無法應用在臺灣。
研究目的
探討加護及重症病房常用靜脈注射藥與furosemide的物理相容性研究，以及探討加護及重症病房常用靜脈注射藥與另一個較安定的環利尿劑bumetanide的物理相容性研究。
研究材料與方法
經由對加護病房中與loop diuretics可能同時給與之藥品的調查以及文獻回顧，共篩選出33種藥品、94組實驗組合。臨床上若藥品以原濃度給藥，則不稀釋；若須稀釋則稀釋液使用5 % dextrose （D5W）及0.9 % NaCl（NS）兩種，除非其一為不相容。濃度則選擇臨床最常用之1或2種濃度。
依Allen等人之模擬Y-site給藥方法，將配製好的藥品經0.22 μm薄膜過濾，取10 mL測量pH值，取20 mL當作對照組，並將利尿劑與其他藥品各取70 mL以1：1等體積混合，置入透明的圓柱型玻璃瓶中，於0-15分鐘、1小時及4小時進行肉眼觀察、pH測量及光阻微粒物質測計法檢驗，並以相反添加順序再測一次0-15分鐘內的結果，以測試相容性的再現性。肉眼觀察到任何變化（不包含廷得耳效應）或是光阻微粒物質測計法結果不符合藥典規定則定義為不相容。
研究結果
Furosemide 10 mg/mL與13種藥品（39.4%）、29組藥品組合（30.9%）產生肉眼可見不相容，以混濁或產生沉澱、懸浮微粒為最常見之變化，唯一產生顏色變化者為metronidazole 5 mg/mL undiluted由無色澄清轉為淺黃色澄清。除肉眼觀察的13種藥品外，另有teicoplanin及lorazepam，共15種藥品（45.5%）、35組藥品組合（37.2%）沒有通過藥典的大體積注射藥品（LVPs）微粒物質檢定（每mL微粒物質≥10 μm者不得大於25個，且每mL微粒物質≥25 μm者不大於3個），幾乎所有不相容混合後可以馬上發現。
Bumetanide 0.5 mg/mL與6種藥品（18.2%）、16組藥品組合（17.0%）產生肉眼可見不相容，以顏色改變為最常見之變化，皆為變成淺黃色澄清。此外，共6種藥品（18.2%）、9組藥品組合（9.6%）沒有通過藥典的大體積注射藥品（LVPs）微粒物質檢定，僅有不到一半比例的不相容藥品對是肉眼立即可觀察到（37.5%），較多變化需要混合1小時後才能觀察到。
33種藥品之中，共有9種藥與furosemide混合會發生不相容，但與bumetanide混合給藥則不會發生；相反的情形則有dopamine HCl及esomeprazole sodium 2種藥品。而33種藥品中，amiodarone HCl、dobutamine HCl、labetalol HCl、lorazepam、nicardipine HCl、teicoplanin共6種藥品在特定濃度及稀釋液條件下對2種loop diuretics都是不相容。
若選擇了2種藥品都相容的稀釋液，則稀釋液的選擇較不會影響到Y-site相容性；而在臨床常用的濃度之下，相容性與濃度也沒有明顯相關；最重要影響相容性的因素為藥品混合前的pH值差異，OR (odds ratio)為1.74 (95% CI=1.36-2.23)，代表若藥品混合前pH值差異每增加1單位，不相容的odds增加74%。
肉眼觀察與微粒物質檢查結果並非完全一致，仍然有藥品混合後是肉眼觀察不出異狀但微粒物質檢查卻未通過，對病人而言可能是潛在的風險，為避免發生不希望的藥品不良事件，建議Y-site相容性研究應使用肉眼觀察配合particle counter進行微粒物質檢測。
結論
Furosemide和ICUs常用藥品高度不相容，應避免與其他藥品一同給與，給藥前後都應以至少5-6倍管內體積的相容稀釋液沖洗管路；若同時給藥無法避免，則有9種藥品在給藥時，furosemide可替換為bumetanide，而非本研究實驗之其餘藥品仍應有文獻證明相容性，且給與後必須觀察有無不相容，尤其是長時間輸注時要特別注意變色等不相容情形發生。

關鍵字

醫藥錯誤 ； furosemide ； bumetanide ； 相容性 ； Y-site

並列摘要

Background
Medication error is the leading cause of treatment failures, harms or deaths. The intravenous (i.v.) medications carry higher risk of medication error than oral medications. Potential physicochemical incompatibilities accounted for up to 25% of medication errors during i.v. administration, and most harms were moderate to severe, even life-threating. According to a study on the computerized physician’s order entry of thirteen intensive care units (ICUs) in National Taiwan University Hospital, four of the ten most frequently encountered incompatible pairs contained furosemide. A literature review on Y-site compatibility of furosemide found that concentration of furosemide and other drugs are different from those used in our hospital. Therefore, these compatibility data cannot be applied in Taiwan.
Objective
To study simulated Y-site physical compatibility of furosemide with selected i.v. medications, and simulated Y-site compatibility of bumetanide with the same selected medications.
Materials and Methods
Through a survey of i.v. drugs used currently with loop diuretics in ICUs and literature review, 33 drugs and 94 pairs were selected. If a drug needs to dilute before administrating, 5 % dextrose and 0.9 % NaCl solution were used, unless one of them is incompatible. All drugs were diluted to one to two most commonly used concentrations.
A simulated Y-site co-administration model develop by Allen et al was adopted. Ten milliliter of each solution was used to measure pH value, and 20 mL as the control. Seventy milliliters of one of the diuretics was mixed with 70 mL of a selective drug in a colorless glass cylinder. All prepared solutions were filtered through a 0.22 μm filter before mixing. After mixing, we inspected the mixture at 0 to 15 minutes, 1 hour and 4 hour by visual inspection, pH measurement and light obscuration particle count test. The order of mixing was reversed and a second inspection was done at 0 to 15 minutes to explore the reproducibility. Any visual change, such as particulate matter, turbidity or color change as compared to the control solutions was defined as incompatible. Mixtures that failed in the particle counter test were also defined as incompatible.
Results
Furosemide 10 mg/mL was visually incompatible with 13 drugs (39.4%) and 29 drug pairs (30.9%). Turbidity, precipitation, particulate formation were the predominant phenomena. Admixture of furosemide and metronidazole 5 mg/mL was the only one that showed color change, which turned from colorless to light yellow. Fifteen drugs (45.5%) and 35 drug pairs (37.2%) failed the particle counter test, including teicoplanin, lorazepam and 13 visually incompatible drugs. All incompatibilities were detected immediately after mixing.
Bumetanide 0.5 mg/mL was visually incompatible with 6 drugs (18.2%) and 16 drug pairs (17.0%), and color change was most frequently observed. Six drugs (18.2%) and 9 drug pairs (9.6%) failed in the particle counter test. Most incompatibility occurred 1 hour after mixing, and only 37.5% were detected immediately.
Nine drugs that were incompatible with furosemide were compatible with bumetanide, while dopamine HCl and esomeprazole sodium had the opposite results. With the specific diluents and concentrations we used, 6 drugs were incompatible with both diuretics, which include amiodarone HCl, dobutamine HCl, labetalol HCl, lorazepam, nicardipine HCl and teicoplanin.
The choice of diluent did not influence Y-site compatibility, if the diluent is compatible with both i.v. drugs. There was no correlation between commonly used concentration and compatibility either. The pH difference between two drugs before mixing was the most important risk factor for incompatibility (OR=1.74, 95% CI=1.36-2.23). For every pH difference increament by 1, the odds of incompatibility increased by 74%.
There were inconsistent results between visual inspection and particle counter tests. Some mixtures passed the visual inspection but failed in the particle test. They may harm the patients. To avoid these unexpected events, particle counter test should be used concurrently with visual inspection in Y-site compatibility study.
Conclusions
Furosemide is highly incompatible with i.v. medications frequently used ICUs, and should not be administered concurrently with other drugs. The intravenous catheter should be flushed at volume of 5 to 6 times the volume of tubing with compatible diluent before and after administering furosemide. There are nine drugs that are incompatible with furosemide but compatible with bumetanide. When co-administration with these 9 drugs is unavoidable, bumetanide may be an alternative of furosemide. However, we must inspect any incompatibility during administering bumetanide, especially color change that may occur during prolonged infusion with other drugs

並列關鍵字

Medication error ； furosemide ； bumetanide ； compatibility ； Y-site

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