Efficacy of continuous vs. intermittent furosemide

Introduction: The pharmacodynamics of furosemide support continuous infusion over bolus administration once a renal threshold is exceeded (1). We evaluated the literature to compare continuous infusion versus the traditional intermittent dosing on the efficiency of diuresis (urine output/mg furosemide). Methods: Studies were identified through MEDLINE, citation review of relevant primary and review articles, and contact with expert informants. We selected randomized clinical trials evaluating continuous versus bolus mode of drug delivery and their effects on urinary output efficiency. Results: We identified five randomized trials comparing continuous (C) versus intermittent (I) dosing of furosemide. Two studies looked at patients with congestive heart failure using a cross-over study design. One study of 20 patients used high dose furosemide (690mg/24hours) and the continuous infusion produced a greater diuresis (2860±240 ml (C) vs 2260±150 ml (I); P= 0.0005) and a significantly greater naturesis. The second study of 9 patients used a lower total dose of furosemide (90 to 120mg/24hours) and the continuous infusion produced a greater diuresis (4490± 443 ml vs. 3790±387 ml; p= 0.01). Three studies were in post-operative cardiac surgical patients. One study in 18 adults comparing 0.3mg/kg in 2 doses versus a drip of 0.05mg/kg/hr found no difference in urinary output (1870±752 (C) vs. 2673±925 (I); NS) or urinary sodium over 12 hours. The majority of the urine volume (70%) was excreted within 2 hours of the intermittent dose. In a second study in 26 stable pediatric post-op patients, a lower total daily dose of continuous furosemide produced identical urine volumes and a smoother diuresis (urine output mean variance 2.19±1.92 ml/kg/day (C) vs. 13.07±14.56 (I), p=0.045). A third study, in 20 post-op pediatric patients requiring inotropic support, used a lower dose of furosemide in the continuous group (4.9mg/kg/day (C) vs. 6.23mg/kg/day (I)). They achieved similar urine output (3.36 ml/kg/day (C) vs. 3.53 ml/kg/day (I)), but a lower net fluid balance in the continuous group (+15.7ml± 4.8 (C) vs. +28.9 ml± 9.0 (1), p<0.04). Conclusion: Continuous infusion of furosemide may be more efficient than bolus dosing in achieving equivalent diuresis at a lower total dose. More consistent diuresis may cause less hemodynamic variability. The minimal dose required to exceed the renal diuresis threshold merits further study.