Effect of bolus injection versus continuous infusion of furosemide on diuresis and neurohormonal activation in patients with severe congestive heart failure. Intermittent administration of furosemide vs continuous infusion preceded by a loading dose for congestive heart failure. Diuretic effects of furosemide infusion versus bolus injection in congestive heart failure. Effects of high-dose furosemide and small-volume hypertonic saline solution infusion in comparison with a high dose of furosemide as bolus in refractory congestive heart failure: long-term effects. Pharmacodynamics of torsemide administered as an intravenous injection and as a continuous infusion to patients with congestive heart failure. Diuretic efficacy of high dose furosemide in severe heart failure: bolus injection versus continuous infusion. Protocol-guided diuretic management: comparison of furosemide by continuous infusion and intermittent bolus.
Previous studies have demonstrated that continuous infusion of furosemide results in increased diuresis and natriuresis compared with bolus administration of the drug in patients with severe heart failure. We reasoned that continuous infusion of furosemide caused less activation of neurohumoral mechanisms, since other studies have shown that bolus administration of furosemide may activate this system. We therefore tested the hypothesis that continuous administration of furosemide would increase water and sodium excretion due to less activation of neurohormones. Eight patients with severe heart failure were studied during continuous infusion over 24 h and bolus injections of furosemide twice daily in a randomized cross-over study. Bolus administration of furosemide increased diuresis and natriuresis significantly in the first 4 h after administration compared with continuous administration, but this was later reversed, resulting in similar 24 h total output. The neurohormones measured at baseline were all markedly elevated. Neither regimens of furosemide caused any further significant changes in neurohumoral response except that pro-ANF decreased more during the first 8 h after bolus administration compared to continuous infusion. This study has demonstrated that bolus administration of furosemide in conventional doses is equally effective as continuous intravenous infusion in patients with severe heart failure. This may be due to maximal neurohormonal activation in severe heart failure (NYHA III-IV) which could not be further activated by bolus administration. Several reports have suggested that continuous intravenous administration of loop diuretics may be superior to intermittent administration. We performed a prospective randomized crossover study comparing intermittent intravenous administration (IA) of furosemide with continuous infusion following a single loading dose (LDCI) in nine patients with severe congestive heart failure. At the time of hospital admission, patients were randomly assigned to one of two treatment groups. One group (four patients) received an IV bolus injection of furosemide followed immediately by a continuous infusion for 48 h. The second group (five patients) was treated with three IV bolus injections a day for 48 h. Total doses of furosemide were equivalent in the two groups. After 48 h, each patient was crossed over to the other method and treated for an additional 48 h. LDCI produced significantly greater diuresis and natriuresis than IA (total urine output increased by 12 to 26 percent, total sodium excretion increased by 11 to 33 percent) (p less than 0.01). There were no significant differences in side effects between the two methods. These results indicate that LDCI may be a preferred method for administration of furosemide in patients with congestive heart failure. In a randomized, single-blind, crossover clinical trial, the diuretic efficacy of the same total dose of furosemide (2 x 40 mg) administered in either conventional intravenous bolus injection or continuous infusion was studied in 20 patients (nine males and 11 females), aged 37-75 years, with congestive heart failure. Furosemide infusion, administered first, produced a significantly greater diuresis than the bolus when compared with baseline (86%: 29.6%; p = 0.029). This was followed by a similar increase in 24-h urinary sodium, potassium and chloride excretion, with no significant difference from the bolus effect. The following day, diuretic and saluretic effects of furosemide did not differ significantly between the study groups. Nevertheless, when continuous furosemide infusion was administered first, it produced a greater increase in urinary volume, 24-h urinary sodium, potassium and chloride than when bolus injection was applied the next day. Conversely, when furosemide bolus was administered first, followed by the infusions the next day, the effects were almost equal, regardless of the mode of administration. It is concluded that in the treatment of refractory edema in patients with congestive heart failure, continuous intravenous infusion of furosemide is superior to the conventional intermittent bolus injection, especially if it is administered at the very beginning of the hospital treatment, and presumably is even better with higher dosage and longer infusion time span. Diuretics have been accepted as first-line treatment in refractory congestive heart failure (CHF), but a lack of response to them is a frequent event. A randomized, single-blind study was performed to evaluate the effects of the combination of high-dose furosemide and small-volume hypertonic saline solution (HSS) infusion in the treatment of refractory New York Heart Association (NYHA) class IV CHF and a normosodic diet during follow-up. Materials and Methods One hundred seven patients (39 women and 68 men, age range 65-90 years) with refractory CHF (NYHA class IV) of different etiologies, who were unresponsive to high oral doses of furosemide, angiotensin-converting enzyme inhibitors, digitalis, and nitrates, were enrolled. Inclusion criteria included an ejection fraction (EF) <35%, serum creatinine level <2 mg/dL, blood urea nitrogen level < or =60 mg/dL, reduced urinary volume, and low natriuresis. The patients were randomized in 2 groups (single-blind). Patients in group 1 (20 women and 33 men) received an intravenous (IV) infusion of furosemide (500-1000 mg) plus HSS (150 mL of 1.4%-4.6% NACl) twice a day in 30 minutes. Patients in group 2 (19 women and 35 men) received an IV bolus of furosemide (500-1000 mg) twice a day, without HSS, during a period lasting 6 to 12 days. Both groups received IV KCl (20-40 mEq) to prevent hypokalemia. At study entry, all patients underwent a physical examination and measurement of body weight (BW), blood pressure (BP), and heart rate (HR), an evaluation of signs of CHF, and measurement of control levels of serum Na, K, Cl, bicarbonate, albumin, uric acid, creatinine, urea, and glycemia daily during hospitalization, and measurements of the daily output of urine for Na, K, and Cl. A chest radiograph, electrocardiogram, and echocardiogram were obtained at study entry, during hospitalization, and at the time of discharge from the hospital. During the treatment and after discharge, the daily dietary Na intake was 120 mmol in group 1 versus 80 mmol in group 2, with a fluid intake of 1000 mL daily in both groups. An assessment of BW and 24-hour urinary volume, serum, and urinary laboratory parameters were performed daily until patients reached a compensated state, when IV furosemide was replaced with oral administration (250-500 mg/d). After discharge from the hospital, patients were observed as outpatients weekly for the first 3 months and, subsequently, once a month.
                The groups were similar in age, sex, EF, risk factors, treatment, and etiology of CHF. All patients showed a clinical improvement. Ten patients in both groups had hyponatremia at entry. A significant increase in daily diuresis and natriuresis was observed in both groups, but it was more significant in the group receiving HSS (P <.05). The serum Na level increased in group 1 and decreased in group 2 (P <.05). The serum K level was decreased in both groups (P <.05). BW was reduced in both groups (P <.05). Group 2 had an increase in serum creatinine level. Serum uric acid levels increased in both groups. BP values decreased and HR was corrected to normal values in both groups. In the follow-up period (31 +/- 14 months), 25 patients from group 1 were readmitted to the hospital for heart failure. In group 2, 43 patients were readmitted to the hospital at a higher class than at discharge. Twenty-four patients in group 1 died during follow-up, versus 47 patients in group 2 (P <.001).
                This treatment is effective and well tolerated, improves the quality of life through the relief of signs and symptoms of congestion, and may delay more aggressive treatments. The effects were also beneficial in a long period for mortality reduction (55% vs 13% survival rate) and for clinical improvement. The natriuretic and diuretic effects of a 100-mg dose of torsemide administered as a continuous infusion of torsemide and as a single bolus were compared in a group of patients with stable mild-to-moderate congestive heart failure (CHF). Patients received in random order 100 mg of torsemide as an intravenous bolus and as a 75-mg infusion over 24 hours started simultaneously with a 25-mg loading bolus. Administration of torsemide to patients with CHF as a continuous infusion was an effective dosing regimen, resulting in 24-hour diuresis and natriuresis that was numerically but not statistically greater than that observed with bolus administration. The response with continuous infusion occurred with less torsemide in the urine, resulting in a significantly greater efficiency of torsemide with this regimen. The effectiveness of torsemide as a continuous infusion does not mean that this mode of administration should be used in all patients. The response to 100 mg of torsemide in patients with mild-to-moderate CHF is the same whether administered as an intravenous bolus, a continuous intravenous infusion, or by mouth. This is consistent with the high bioavailability demonstrated in previous studies. The mode of therapy used should be dictated by each individual patient's needs. This study shows that continuous infusion is a viable option for administration of torsemide, and dosing guidelines for use of such a strategy are presented. The efficacy of high dose furosemide as a continuous infusion was compared with a bolus injection of equal dose in patients with severe heart failure.
                The delivery rate of furosemide into the nephron has been proved to be a determinant of diuretic efficacy in healthy volunteers.
                In a randomized crossover study we compared the efficacy of a continuous infusion of high dose furosemide (mean daily dosage 690 mg, range 250 to 2,000) versus a single bolus injection of an equal dose in 20 patients with severe heart failure. The patients received an equal dosage, either as a single intravenous bolus injection or as an 8-h continuous infusion preceded by a loading dose (20% of total dosage).
                Mean (+/- SEM) daily urinary volume (infusion 2,860 +/- 240 ml, bolus 2,260 +/- 150 ml, p = 0.0005) and sodium excretion (infusion 210 +/- 40 mmol, bolus 150 +/- 20 mmol, p = 0.0045) were significantly higher after treatment with continuous infusion than with bolus injection, despite significantly lower urinary furosemide excretion (infusion 310 +/- 60 mg every 24 h, bolus 330 +/- 60 mg every 24 h, p = 0.0195). The maximal plasma furosemide concentration was significantly higher after bolus injection than during continuous infusion (infusion 24 +/- 5 micrograms/ml, bolus 95 +/- 20 micrograms/ml, p < 0.0001). Short-term, completely reversible hearing loss was reported only after bolus injection in 5 patients.
                We conclude that in patients with severe heart failure, high dose furosemide administered as a continuous infusion is more efficacious than bolus injection and causes less ototoxic side effects. To evaluate the safety and relative effectiveness of two diuretic protocols in the intensive care unit (ICU).
                Prospective, randomized comparative study.
                Thirty-three cardiac and medical ICU patients with pulmonary edema or fluid overload for which aggressive diuresis was intended.
                Enrolled patients were randomized to fluid management strategies combining fluid restriction and individually adjusted diuretic therapy by either continuous or bolus infusions of furosemide, titrated to achieve negative hourly fluid balance.
                Cumulative intake minus output (primary endpoint); change in serum creatinine, and length of ICU and hospital stay (secondary endpoints). Diuresis by either protocol was feasible, safe, and effective. The main outcome measures were not significantly different for either group managed with a standardized protocol.
                Protocol-guided diuretic management, with individualized titration of dosage to defined physiologic endpoints can be readily and safely implemented in the ICU. Both continuous and bolus diuretic regimens appear equally effective in achieving negative fluid balance. Larger studies with a randomized control arm are needed before these protocols can be recommended as routine practice.
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.