Cochrane 資料庫在2009年發表了一篇綜合分析的文章--Continuous infusion versus bolus injection of loop diuretics in congestive heart failure--
Background: Loop diuretics, when given as intermittent bolus injections in acutely decompensated heart failure, may cause fluctuations in intravascular volume, increased toxicity and development of tolerance. Continuous infusion has been proposed to avoid these complications and result in greater diuresis, hopefully leading to faster symptom resolution, decrease in morbidity and possibly, mortality. Objectives:To compare the effects and adverse effects of continuous intravenous infusion of loop diuretics with those of bolus intravenous administration among patients with congestive heart failure Class III-IV.
Search strategy: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2, 2003), MEDLINE (1966 to 2003), EMBASE (1980 to 2003) and the HERDIN database. We also contacted pharmaceutical companies .
Selection criteria:Randomized controlled trials comparing the efficacy of continuous intravenous infusion versus bolus intravenous administration of loop diuretics in congestive heart failure were included Data collection and analysis:Two reviewers independently assessed study eligibility, methodological quality and did data extraction. Included studies were assessed for validity. Authors were contacted when feasible. Adverse effects information was collected from the trials.
Main results:Eight trials involving 254 patients were included. In seven studies which reported on urine output, the output (as measured in cc/24 hours) was noted to be greater in patients given continuous infusion with a weighted mean difference (WMD) of 271 cc/24 hour (95%CI 93.1 to 449; p<0.01). Electrolyte disturbances (hypokalemia, hypomagnesemia) were not significantly different in the two treatment groups with a relative risk (RR) of 1.47 (95%CI 0.52 to 4.15; p=0.5). Less adverse effects (tinnitus and hearing loss) were noted when continuous infusion was given, RR 0.06 (95%CI 0.01 to 0.44; p=0.005). Based on a single study, the duration of hospital stay was significantly shortened by 3.1days with continuous infusion WMD -3.1 (95%CI -4.06 to -2.20; p<0.0001) while cardiac mortality was significantly different in the two treatment groups, RR 0.47 (95% CI 0.33 to 0.69; p<0.0001). Based on two studies, all cause mortality was significantly different in the two treatment groups, RR 0.52 (95%CI 0.38 to 0.71; p<0.0001).(持續性輸注尿量較多，每日可較bolus組多271ml，電解質異常兩組無差異，較低的副作用-耳鳴/聽力喪失(危險比0.06); 根據一項單一研究，持續性輸注組可縮短住院天數3.1天，心臟死亡風險低(0.47);根據2篇研究結果，所有原因死亡風險低(0.52)。
Authors' conclusions: Currently available data are insufficient to confidently assess the merits of the two methods of giving intravenous diuretics. Based on small and relatively heterogenous studies, this review showed greater diuresis and a better safety profile when loop diuretics were given as continuous infusion. The existing data still does not allow definitive recommendations for clinical practice and larger studies should be done to more adequately settle this issue.(目前可獲得ㄉ資料仍不充分來評估兩種給藥途徑的價值，根據小規模及相對異質性的研究，結果顯示給予連續輸注利尿劑有較多的尿量及較好的安全性，目前的資料仍然無法明確推薦在臨床上，須大規模研究再釐清這些爭議)。 adapted from http://onlinelibrary.wiley.com/o/cochrane/clsysrev/articles/CD003178/frame.html
今年2011 NEJM 發表了一篇Diuretic Strategies in Patients with Acute Decompensated Heart Failure
研究方法: In a prospective, double-blind, randomized trial, we assigned 308 patients with acute decompensated heart failure to receive furosemide administered intravenously by means of either a bolus every 12 hours or continuous infusion and at either a low dose (equivalent to the patient’s previous oral dose) or a high dose (2.5 times the previous oral dose). The protocol allowed specified dose adjustments after 48 hours. The coprimary end points were patients’ global assessment of symptoms, quantified as the area under the curve (AUC) of the score on a visual-analogue scale over the course of 72 hours, and the change in the serum creatinine level from baseline to 72 hours.(前瞻雙盲隨機實驗，308位病人隨機給予lasix q12h 或 連續性輸注 及 低劑量(相當於病患之前口服劑量) 或 高劑量 (
相當於2.5倍病患之前口服劑量)，48小時後准許指定劑量調整。共同實驗終點是在72小時整體症狀評估及 creatinine 的改變量。
global assessment of symptoms(整體症狀評估)--使用一個視覺模擬評分法，病患從一個0至10公分的垂直線，去指出目前症狀的狀況，分數越大代表感覺越好，分數越低感覺越差，記錄者用0~100分去記錄。整體症狀評估從一開始至72小時使用AUC(截面積下)評估總分。
結果:bolus VS 持續輸注 整體症狀評估分數並無統計上的差異。bolus VS 持續輸注 在第48小時需增加劑量(21% vs. 11%, P = 0.01)。三天lasix總劑量在bolus為592mg與持續輸注480mg無差異，bolus VS 持續輸注 在第48小時可能需轉換成口服劑量，兩組是無差異。bolus VS 持續輸注 在 72小時期間Cre平均改變量是兩組無統計學上的差異。
低劑量VS高劑量 在第48小時高劑量較可能改成口服劑量(31% vs. 17%, P<0.001)， 在第48小時低劑量較有可能增加50%劑量(24% vs. 9%,P = 0.003)，三天lasix總劑量在低劑量為358mg與高劑量773mg有差異(P<0.001)，高劑量組在整體症狀評估分數有較高的趨勢但無統計上的差異，在 72小時期間Cre平均改變量是兩組無統計學上的差異。
次要實驗終點: bolus VS 持續輸注 在次要實驗項目無統計學上的差異。低劑量VS高劑量，高劑量可造成較佳的喘改善，體重減輕，尿量輸出量增加，不過潛在的效益可能會被高劑量組所造成腎功能的惡化(72小時內Cre>0.3mg/dl)所抵銷。高劑量組有較少的嚴重不良事件(38% vs. 50%, P = 0.03)。
治療失敗的定義:as the development of any one of the following during the 72 hours after randomization: increase in serum creatinine level of more than 0.3 mg per deciliter (26.5 μmol per liter), worsening or persistent heart failure, clinical evidence of excessive diuresis requiring intervention (e.g., administration of intravenous fluids), or death.
結論:在急性失代償性心衰竭病患，無論是blous vs 持續輸注 或是 低劑量 vs 高劑量組，在整體症狀及Cre平均改變量兩組都無統計學上的差異。