Continuous versus intermittent administration of furosemide in acute decompensated heart failure: a systematic review and meta-analysis

Diuretic therapy is important in critically ill patients because fluid overload impairs organ function and increases mortality. Compared to intermittent administration, continuous infusion of loop diuretics is theoretically superior in terms of diuresis and electrolyte balance. However, the available evidence is susceptible to carryover diuretic effects and resistance in earlier crossover trials. Consequently, we conducted a systematic review and meta-analysis of parallel-group randomized controlled trials to compare these two strategies in adults with acute decompensated heart failure. We searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials from their inceptions to May 26, 2018. We pooled the data using a random effects model. Our primary outcomes were all-cause mortality, length of hospital stay, and body weight reduction. We analyzed 12 parallel-group randomized controlled trials involving 923 patients. Compared with intermittent administration, continuous infusion of furosemide was not associated with an improvement in all-cause mortality (risk ratio 1.19; 95% confidence interval [CI], 0.65 to 2.16), length of hospital stay (weighted mean difference [WMD] -0.88 days; 95% CI, -2.76 to 1.01), or 24-h urine output (WMD 489.17 mL; 95% CI, -183.18 to 1161.51), but was significantly associated with a greater body weight reduction (WMD 0.63 kg; 95% CI, 0.23 to 1.02). No differences in hypokalemia, hyponatremia, increased serum creatinine level, and hypotension were noted. Continuous infusion of furosemide, compared to intermittent administration, is associated with a greater body weight reduction and potential increase in 24-h urine output. The limited available evidence suggests no difference in adverse events between both strategies.