PMID- 26521190 OWN - NLM STAT- MEDLINE DCOM- 20160615 LR - 20220310 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 32 IP - 10 DP - 2015 Oct TI - Hypertonic Saline in Conjunction with High-Dose Furosemide Improves Dose-Response Curves in Worsening Refractory Congestive Heart Failure. PG - 971-82 LID - 10.1007/s12325-015-0254-9 [doi] AB - INTRODUCTION: Diuretic responsiveness in patients with chronic heart failure (CHF) is better assessed by urine production per unit diuretic dose than by the absolute urine output or diuretic dose. Diuretic resistance arises over time when the plateau rate of sodium and water excretion is reached prior to optimal fluid elimination and may be overcome when hypertonic saline solution (HSS) is added to high doses of furosemide. METHODS: Forty-two consecutively hospitalized patients with refractory CHF were randomized in a 1:1:1 ratio to furosemide doses (125 mg, 250 mg, 500 mg) so that all patients received intravenous furosemide diluted in 150 ml of normal saline (0.9%) in the first step (0-24 h) and the same furosemide dose diluted in 150 ml of HSS (1.4%) in the next step (24-48 h) as to obtain 3 groups as follows: Fourteen patients receiving 125 mg (group 1), fourteen patients receiving 250 mg (group 2), and fourteen patients receiving 500 mg (group 3) of furosemide. Urine samples of all patients were collected at 30, 60, and 90 min, and 3, 4, 5, 6, 8, and 24 h after infusion. Diuresis, sodium excretion, osmolality, and furosemide concentration were evaluated for each urine sample. RESULTS: After randomization, 40 patients completed the study. Two patients, one in group 2 and one in group 3 dropped out. Patients in group 1 (125 mg furosemide) had a mean age of 77 +/- 17 years, 43% were male, 6 (43%) had heart failure with a preserved ejection fraction (HFpEF), and 64% were in New York Heart Association (NYHA) class IV; the mean age of patients in group 2 (250 mg furosemide) was 80 +/- 8.1 years, 15% were male, 5 (38%) had HFpEF, and 84% were in NYHA class IV; and the mean age of patients in group 3 (500 mg furosemide) was 73 +/- 12 years, 54% were male, 6 (46%) had HFpEF, and 69% were in NYHA class IV. HSS added to furosemide increased total urine output, sodium excretion, urinary osmolality, and furosemide urine delivery in all patients and at all time points. The percentage increase was 18,14, and 14% for urine output; 29, 24, and 16% for total sodium excretion; 45, 34, and 20% for urinary osmolarity; and 27, 36, and 32% for total furosemide excretion in groups 1, 2, and 3, respectively. These findings were translated in an improvement in the furosemide dose-response curves in these patients. CONCLUSION: These results may serve as new pathophysiological basis for HSS use in the treatment of refractory CHF. FAU - Paterna, Salvatore AU - Paterna S AD - Dipartimento Biomedico di Medicina Interna e Specialistica (DIBIMIS), AOUP "Paolo Giaccone" Universita degli Studi di Palermo, Palermo, Italy. FAU - Di Gaudio, Francesca AU - Di Gaudio F AD - Dipartimento Biopatologia e Biotecnologie Mediche e Forensi (DiBiMEF), AOUP "Paolo Giaccone" Universita degli Studi di Palermo, Palermo, Italy. FAU - La Rocca, Vincenzo AU - La Rocca V AD - Dipartimento Energia, Ingegneria dell'Informazione e Modelli Matematici (DEIM), Universita degli Studi di Palermo, Palermo, Italy. FAU - Balistreri, Fabio AU - Balistreri F AD - Dipartimento Biomedico di Medicina Interna e Specialistica (DIBIMIS), AOUP "Paolo Giaccone" Universita degli Studi di Palermo, Palermo, Italy. FAU - Greco, Massimiliano AU - Greco M AD - Dipartimento Biopatologia e Biotecnologie Mediche e Forensi (DiBiMEF), AOUP "Paolo Giaccone" Universita degli Studi di Palermo, Palermo, Italy. FAU - Torres, Daniele AU - Torres D AD - Dipartimento Biomedico di Medicina Interna e Specialistica (DIBIMIS), AOUP "Paolo Giaccone" Universita degli Studi di Palermo, Palermo, Italy. FAU - Lupo, Umberto AU - Lupo U AD - Dipartimento Biomedico di Medicina Interna e Specialistica (DIBIMIS), AOUP "Paolo Giaccone" Universita degli Studi di Palermo, Palermo, Italy. FAU - Rizzo, Giuseppina AU - Rizzo G AD - UO Medicina D'Urgenza e Pronto Soccorso AOUP "Paolo Giaccone" Universita degli Studi di Palermo, Palermo, Italy. FAU - di Pasquale, Pietro AU - di Pasquale P AD - UO di Cardiologia "Paolo Borsellino", Ospedale GF Ingrassia Palermo, Palermo, Italy. FAU - Indelicato, Sergio AU - Indelicato S AD - Dipartimento Biopatologia e Biotecnologie Mediche e Forensi (DiBiMEF), AOUP "Paolo Giaccone" Universita degli Studi di Palermo, Palermo, Italy. FAU - Cuttitta, Francesco AU - Cuttitta F AD - Dipartimento Biomedico di Medicina Interna e Specialistica (DIBIMIS), AOUP "Paolo Giaccone" Universita degli Studi di Palermo, Palermo, Italy. FAU - Butler, Javed AU - Butler J AD - Cardiology Division, Stony Brook University, Stony Brook, NY, USA. FAU - Parrinello, Gaspare AU - Parrinello G AD - Dipartimento Biomedico di Medicina Interna e Specialistica (DIBIMIS), AOUP "Paolo Giaccone" Universita degli Studi di Palermo, Palermo, Italy. gaspare.parrinello@unipa.it. LA - eng PT - Journal Article PT - Randomized Controlled Trial DEP - 20151031 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 0 (Diuretics) RN - 0 (Saline Solution, Hypertonic) RN - 7LXU5N7ZO5 (Furosemide) RN - 9NEZ333N27 (Sodium) MH - Aged MH - Aged, 80 and over MH - Chronic Disease MH - Diuretics/administration & dosage/*therapeutic use MH - Dose-Response Relationship, Drug MH - Drug Therapy, Combination MH - Drug Tolerance MH - Female MH - Furosemide/administration & dosage/*therapeutic use MH - Heart Failure/*drug therapy MH - Humans MH - Male MH - Middle Aged MH - Osmolar Concentration MH - Saline Solution, Hypertonic/administration & dosage/*therapeutic use MH - Sodium/urine PMC - PMC4635178 OTO - NOTNLM OT - Dose-response curves OT - Furosemide OT - Heart failure OT - Hypertonic saline OT - Refractory chronic heart failure EDAT- 2015/11/02 06:00 MHDA- 2016/06/16 06:00 PMCR- 2015/10/31 CRDT- 2015/11/02 06:00 PHST- 2015/09/09 00:00 [received] PHST- 2015/11/02 06:00 [entrez] PHST- 2015/11/02 06:00 [pubmed] PHST- 2016/06/16 06:00 [medline] PHST- 2015/10/31 00:00 [pmc-release] AID - 10.1007/s12325-015-0254-9 [pii] AID - 254 [pii] AID - 10.1007/s12325-015-0254-9 [doi] PST - ppublish SO - Adv Ther. 2015 Oct;32(10):971-82. doi: 10.1007/s12325-015-0254-9. Epub 2015 Oct 31.