A controlled trial found that in patients with acute decompensated congestive heart failure (CHF), outcomes were similar with administration by IV bolus and continuous infusion of furosemide, and similar whether the dose was the patient’s previous oral dose or 2.5 times that.

Acute CHF is a common reason for hospital admission of elderly patients, and IV loop diuretics are a well-established mainstay of treatment. There is, however, limited prospective evidence to show how these drugs can best be used and both method of administration and dose vary. Some evidence suggests that continuous infusion may be preferable to bolus dosing, and high doses might be more effective but are known to have the potential for adverse effects especially on renal function. The aim of this North American multi-centre trial was to clarify the issue by comparing standard vs. high dose, and continuous vs. bolus injection.

Participants were patients with acute decompensated CHF within 24 hours of presentation who had a past history of chronic CHF and were previously using a loop diuretic at a dose of 40mg to 240mg furosemide daily or equivalent. They were randomised to IV furosemide in low dose (total daily dose equivalent to previous daily oral loop diuretic dose as furosemide) or high-dose (dose 2.5 times previous oral dose) strategies, administered either by continuous infusion or as IV bolus in two divided doses given at 12-hour intervals. A double-blind, double-dummy design was used to ensure blinding. Two primary outcome measures were used: for efficacy, the 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 for safety, the change in the serum creatinine level from baseline to 72 hours.

In total, 308 patients were randomised by 26 centres over a 20-month period. About three-quarters were male, their mean age was about 66, and their mean oral dose of loop diuretic was about 130mg furosemide or equivalent daily. In the comparison of administration methods, there were no significant differences between bolus and continuous infusion in either symptoms (mean AUC, 4236±1440 and 4373±1404, respectively; P=0.47) or in the mean change in the creatinine level (4.4±26.5 and 0.07±0.3 micromol/l respectively; P=0.45).

There were also no significant differences between the high-dose and low-dose groups in the primary outcomes, although there was a non-significant trend in favour of high-dose for symptoms (mean AUC, 4430±1401 vs. 4171±1436; P=0.06) with no significant difference for safety (7.1±26.5 vs. 3.5±26.5 micromol/l respectively, P=0.21). Compared to the low dose strategy, higher doses were associated with improvements in some secondary efficacy outcomes (net fluid loss, weight loss, and relief from dyspnoea), but also with transient worsening in one of the secondary endpoints (renal function).

The authors conclude that in patients with acute decompensated CHF, there was no difference between IV loop diuretic administered as continuous infusion or 12-hourly bolus. They comment that this is contrary to the findings of previous, but much smaller trials, and note possible reasons for this. The high-dose strategy was not associated with significant benefits in the primary outcome, but neither was there a significant difference in the safety outcome. Secondary outcomes suggested possible benefits from higher doses in more rapid symptom relief, particularly dyspnoea, and although there was an increased risk of transient worsening of renal function this did not affect outcomes at 60 days.

An accompanying editorial discusses the study. The author welcomes the study, noting that there is little controlled trial evidence on the use of these drugs in acute CHF. He suggests that its results support the use of bolus injections as being more convenient and equally effective, and that higher doses are preferred as giving better symptom relief without significant added toxicity.