Ferguson J A, Sundblad K J, Becker P K, Gorski J C, Rudy D W, Brater D C
Department of Medicine, Indiana University School of Medicine, USA.
Clin Pharmacol Ther. 1997 Aug;62(2):203-8. doi: 10.1016/S0009-9236(97)90069-2.
To determine whether the duration of diuretic effect at the active nephron site enhances ability to excrete an exogenous salt load.
We conducted a study that involved eight patients with New York Heart Association class II to III congestive heart failure. In a randomized, crossover manner, each patient received 3.25 mg intravenous bumetanide at 0 hours and again at 6 hours or a loading dose of 0.5 mg bumetanide at 0 hours followed by a continuous infusion of 0.5 mg/hr for 6 hours. Response was followed for 12 hours; a total of 6.5 mg of bumetanide was administered in each arm of the study. Eight hours after dosing began, we administered approximately 80 mEq sodium intravenously and examined its excretion over 4 hours.
The percentage of the load excreted was 86% +/- 15% versus 29% +/- 30% for the infusion and bolus regimens, respectively (p = 0.0005). More bumetanide was excreted during the infusion (667 +/- 133 micrograms versus 240 +/- 121 micrograms; p = 0.0002). During the infusion, however, more sodium was excreted relative to amounts of bumetanide, indicating that the efficiency of response was greater during the infusion, 0.10 +/- 0.02 mEq sodium per microgram bumetanide versus 0.07 +/- 0.05 mEq for the bolus (p = 0.0145).
These data support the notions that a long-acting loop diuretic maintains its efficacy and that a longer duration of action facilitates excretion of a sodium load, such as that which might occur during dietary indiscretion.
确定活性肾单位部位利尿作用的持续时间是否能增强机体排泄外源性盐负荷的能力。
我们开展了一项研究,纳入了8例纽约心脏协会心功能II至III级的充血性心力衰竭患者。采用随机交叉方式,每位患者在0小时静脉注射3.25毫克布美他尼,6小时后再次注射;或在0小时给予0.5毫克布美他尼的负荷剂量,随后以0.5毫克/小时的速度持续输注6小时。观察反应12小时;研究的每个组均给予总共6.5毫克布美他尼。给药开始8小时后,我们静脉注射约80毫当量钠,并在4小时内检查其排泄情况。
输注方案和推注方案排出的负荷百分比分别为86%±15%和29%±30%(p = 0.0005)。输注期间排出的布美他尼更多(667±133微克对240±121微克;p = 0.0002)。然而,在输注期间,相对于布美他尼的量,排出的钠更多,这表明输注期间的反应效率更高,每微克布美他尼排出0.10±0.02毫当量钠,而推注为0.07±0.05毫当量(p = 0.0145)。
这些数据支持以下观点,即长效袢利尿剂可维持其疗效,且作用持续时间延长有助于钠负荷的排泄,如饮食不当期间可能发生的情况。