Effects of high-dose furosemide and small-volume hypertonic saline solution infusion in comparison with a high dose of furosemide as a bolus, in refractory congestive heart failure

Background: Diuretics, have been accepted as first-line treatment in refrac tory heart failure, but a lack of response is a frequent event. A randomise d single blind study was performed to evaluate the effects of the combinati on of high-dose furosemide and small-volume hypertonic saline solution (HSS ) infusion in the treatment of refractory NYHA class IV congestive heart fa ilure (CHF). Materials and methods: Sixty patients (21 F/39 M) with refract ory CHF (NYHA class IV) of different etiologies, unresponsive to high oral doses of furosemide, ACE-inhibitors, digitalis, and nitrates, aged 65-90 ye ars, were enrolled. They had to have an ejection fraction (EF) < 35%, serum creatinine < 2 mg/dl, BUN less than or equal to 60 mg/dl, a reduced urinar y volume and a low natriuresis. The patients were randomised in two groups (single blind): group 1 (11 F/19 M) received an i.v. infusion of furosemide (500-1000 mg) plus HSS (150 ml of 1.4-4.6% NaCl) b.i.d, in 30 min. Group 2 (10 F/20 M) received an i.v. bolus of furosemide (500-1000 mg) b.i.d., wit hout HSS, during a period lasting 6-12 days. Both groups received KCl (20-4 0 mEq.) i.v. to prevent hypokalemia. All patients underwent at entry a phys ical examination, measurement of body weight (BW), blood pressure (BP), hea rt rate (HR), evaluation of signs of CHF, and controls of serum Na, K, Cl, bicarbonate, albumin, uric acid, creatinine, urea and glycemia and daily du ring hospitalization, as well as the daily output of urine for, Na, K and C l measurements. Chest X-ray, ECG and echocardiogram were obtained at entry during and at the discharge. During the treatment and after discharge the d aily dietary Na intake was 120 mmol with a drink fluid intake of 1000 mi da ily. An assessment of BW and 24-h urinary volume, serum and urinary laborat ory parameters, until reaching a compensated state, were performed daily, w hen i.v, furosemide was replaced with oral administration (250-500 mg/day). After discharge, patients were followed as outpatients weekly for the firs t 3 months and subsequently once per month. Results: The groups were simila r for age, sex, EF, risk factors, treatment and etiology of CHF. All patien ts showed a clinical improvement. Six patients in both groups had hyponatre mia (from 120 to 128 mEq./1) at entry. A significant increase in daily diur esis in both groups was observed (from 390 +/- 155 to 2100 +/- 626, and fro m 433 +/- 141 to 1650 +/- 537 ml/24 h, P < 0.05). Natriuresis (from 49 +/- 15 to 198 +/- 28 mEq./24 h) was higher in group 1 vs. group 2 (from 53.83 /- 12 to 129 +/- 39 mEq./24 h, P < 0.05). Serum Na (from 135.9 +/- 6.8 to 1 42.2 +/- 3.8 mEq./1, P < 0.05) increased in the group 1 and decreased in th e group 2 (from 134.7 +/- 7.9 to 130.1 +/- 4.3 mEq./1). Serum K was decreas ed (from 4.4 +/- 0.6 to 3.9 +/- 0.6, and 4.6 +/- 9 to 3.6 +/- 0.5 mEq./1, P < 0.05) in both groups. BW was reduced (from 73.8 +/- 9.1 to 63.8 +/- 8.8, and from 72.9 +/- 10.2 to 64.5 +/- 7.5 kg, P < 0.05) in both groups. Group 2 showed more patients in NYHA class III than group 1 (18 vs. 2 patients, P < 0.05). Group 2 showed an increase of serum creatinine. Serum uric acid increased in both groups. BP values decreased, and HR was corrected to norm al values in both groups. Group 2 showed a longer hospitalization time than group receiving HHS infusion (11.67 +/- 1.8 vs. 8.57 +/- 2.3 days, P < 0.0 01). In the follow-up (6-12 months), none of the patients from group 1 were readmitted to the hospital and they maintained the NYHA class achieved at the discharge. Group 2 showed 12 patients readmitted to hospital and a high er class than at discharge. Conclusion: Our data suggest that the combination of furosemide with HSS is feasible and it appears that this combination produces an improvement of h emodynamic and clinical parameters, reduces the hospitalization time and ma intains the obtained results over time in comparison with those receiving h igh-dose furosemide as bolus. (C) 2000 European Society of Cardiology. All rights reserved.