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Controlled decongestion by Reprieve therapy in acute heart failure: results of the TARGET-1 and TARGET-2 studies.
Biegus, J, Zymlinski, R, Siwolowski, P, Testani, J, Szachniewicz, J, Tycińska, A, Banasiak, W, Halpert, A, Levin, H, Ponikowski, P
European journal of heart failure. 2019;(9):1079-1087
Abstract
AIMS: Safe and effective decongestion is the main goal of therapy in acute heart failure (AHF). In the non-randomized, prospective TARGET-1 and TARGET-2 studies (NCT03897842), we investigated whether adding the Reprieve System® (which continuously monitors urine output and delivers a matched volume of hydration fluid sufficient to maintain the set fluid balance rate) to standard diuretic-based regimen improves decongestion in AHF. METHODS AND RESULTS The population consisted of 19 patients hospitalized with AHF (mean age 67 ± 10 years, 18 male, ejection fraction 34 ± 15%, median N-terminal pro-B-type natriuretic peptide 4492 pg/mL). Patients served as their own controls: each patient underwent 24 h of standard diuretic therapy followed by 24 h of diuretics with Reprieve therapy (with normal saline used for matched volume replacement). The primary efficacy endpoint of actual fluid loss not exceeding the target fluid loss at the end of therapy was met in all 19 (100%) patients. The mean diuresis during Reprieve therapy was 6284 ± 2679 mL (vs. 1966 ± 1057 mL 24 h before therapy) and 2053 ± 888 mL (24 h after therapy) (both P < 0.0001). At the end of therapy, patient global assessment improved from 7.7 ± 1.1 to 3.0 ± 1.3 points (P < 0.001), central venous pressure decreased from 15.5 ± 5.3 mmHg to 12.8 ± 4.8 mmHg (P < 0.05) and the median urine sodium loss was 9.7 [3-13] mmol/h. The Reprieve therapy was safe, systolic blood pressure remained stable, mean creatinine dropped from 1.45 ± 0.4 mg/dL to 1.26 ± 0.4 mg/dL (P < 0.001) and biomarkers of renal injury did not change during treatment. CONCLUSIONS The Reprieve System in conjunction with diuretic therapy supports safe and controlled decongestion in AHF.
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Early and personalized ambulatory follow-up to tailor furosemide and fluid intake according to congestion in post-discharge heart failure.
Parrinello, G, Torres, D, Paterna, S, Di Pasquale, P, Trapanese, C, Cardillo, M, Bellanca, M, Fasullo, S, Licata, G
Internal and emergency medicine. 2013;(3):221-8
Abstract
Congestive heart failure (CHF) worsening is a worldwide cause of rehospitalization and mortality, specially during the early period after hospitalization. Fluid accumulation plays a key role in the pathophysiology of both acute heart decompensation and disease progression. The effective use of drugs to maintain restored clinical stabilization in recently discharged patients is a difficult task, and it relies on matching the most appropriately tailored therapy to specific clinical profiles. However, no successful treatment has been shown to reduce post-discharge readmission. We evaluated in a case-control study the effectiveness of an early and personalized congestion-guided ambulatory program on medium-term (6 months) compensation in recently discharged CHF patients. Group A (22 patients) underwent a post-discharge close follow-up consisting of: an early clinic visit within 10 days; a second visit within 10 days after the first; and the other visits at month 1, 2, 3 after discharge. Controls (Group B, 21 patients) underwent a conventional ambulatory follow-up only at month 1, 2, 3 after discharge. The ambulatory approach in both groups was based on the monitoring of signs/symptoms of congestion and body weight, body hydration estimation by using bioelectrical impedance analysis (BIA) and laboratory data. This assessment was finalized to tailor furosemide and daily fluid intake at each visit to eliminate clinical or instrumental evidence of persistent congestion relieving the signs and symptoms. At 6 months, Group A was associated with a better clinical compensation (improved hydration state, lower BNP levels and congestion score), an improved quality of life, and reduced re-hospitalizations. We conclude that in CHF the early and personalized ambulatory follow-up based on congestion-guided treatment is effective to optimize management and maintain clinical stability in the post-discharge period.
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Continuous renal replacement therapy versus furosemide for management of kidney impairment in heart transplant recipients with volume overload.
Mirhosseini, SM, Fakhri, M, Asadollahi, S, Ahmadi, ZH, Rashid Farokhi, F, Boloursaz, MR, Masjedi, MR
Interactive cardiovascular and thoracic surgery. 2013;(3):314-20
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Abstract
OBJECTIVES It is unknown whether continuous renal replacement therapy or furosemide therapy is superior in heart transplant recipients who are in postoperative kidney insufficiency and volume overload. This prospective non-randomized, controlled trial investigated the efficacy of the two methods after transplantation. METHODS We assigned heart transplant recipients 18 years of age or older who were oliguric (urine output < 400 ml/day); had volume overload and estimated glomerular filtration rate <60 ml/min/1.73 m(2) of body surface area calculated with the use of the Modification of Diet in Renal Disease equation, to designed initiation of intervention. We followed 30 patients for up to 30 days. The primary outcome was estimated glomerular filtration rate status after intervention. RESULTS Between January 2010 and April 2012, a total of 30 adults (mean age: 37 years; 18 men and 12 women) were assessed for entry in this trial. Continuous renal replacement therapy, when compared with furosemide, was associated with a significant increase in estimated glomerular filtration rate of patients after intervention 61 ± 4.5 vs 55 ± 8.5l ml/min/1.73 m(2) (P = 0.02). Moreover, the mean glomerular filtration rate at discharge time for the continuous renal replacement therapy group was 72 ± 7.3 and 58 ± 7.4 ml/min/1.73 m(2) for the furosemide group (P < 0.001). During the follow-up period, 6 of 15 patients in the continuous renal replacement therapy group (40%) and 4 of 15 in the furosemide group (26.6%) died (P = 0.43). CONCLUSIONS In this study, continuous renal replacement therapy in heart transplant recipients with reduced kidney function was associated with an improvement in estimated glomerular filtration rate status in comparison with furosemide.
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Recombinant human TSH and ablation of post-surgical thyroid remnants in differentiated thyroid cancer: the effect of pre-treatment with furosemide and furosemide plus lithium.
Barbaro, D, Grosso, M, Boni, G, Lapi, P, Pasquini, C, Orsini, P, Turco, A, Meucci, G, Marzola, MC, Berti, P, et al
European journal of nuclear medicine and molecular imaging. 2010;(2):242-9
Abstract
BACKGROUND AND AIM Recombinant human TSH (rhTSH) can be used for post-surgical radioiodine (I-131) thyroid remnants ablation in differentiated thyroid cancer (DTC) patients after surgery. Debate exists in literature about the optimal amount of I-131 that should be given for obtaining an effective ablation and about the role of iodine pool during treatment. Therefore, the aim of the present study was to assess whether I-131 ablation during rhTSH stimulus can be improved by reducing the circulating iodine pool and by increasing thyroid cell uptake and retention of I-131 obtained by administering furosemide and lithium. METHODS A total of 201 consecutive DTC patients were entered in the study: they were treated by total thyroidectomy and I-131 therapy during rhTSH stimulus to ablate thyroid remnants. Patients were divided into two groups according to the TNM stage: group 1 included patients in stage I-II who were treated with a low 30-mCi I-131 dose, while group 2 included patients in stage III-IV who were treated by a high 100-mCi I-131 dose. Moreover, both groups were further subdivided into three subgroups. Subgroup (a) included 45 patients from group 1 and 22 from group 2: they were treated with I-131 under rhTSH stimulus, following a short 4-day withdrawal of L-thyroxine (LT4). Subgroup (b) included 45 patients from group 1 and 22 from group 2: they were treated with I-131 under rhTSH stimulus, following a short 4-day withdrawal of L-T4, and after furosemide administration (25 mg/day orally) during the 3 days before I-131. Subgroup (c) included 45 patients from group 1 and 22 from group 2: they were treated with I-131 under rhTSH stimulus, following a short 4-day L-T4 withdrawal, and after administration of furosemide (25 mg/day orally) during the 3 days prior I-131 and lithium (450 mg/day orally) during the 3 days following I-131. Another group (group 3) of 20 patients characterized by a very low-risk cancer (unifocal tumor <1.0 cm in diameter, without extra-capsular extension, N0) was treated with a 30-mCi I-131 dose under rhTSH stimulus without performing the short 4-day L-4 withdrawal: this group was taken as the control. Follow-up was performed by neck ultrasonography (US), and Tg measurement and I-131 WBS under rhTSH stimulus. RESULTS Among the patients from group 1, those pre-treated with furosemide or with furosemide plus lithium showed a better outcome of ablation both in terms of undetectable Tg values (97.7% and 95.5 % vs. 79.5%, p < 0.05) and of WBS negativity (97.7% vs. 81.8%, p < 0.05) during the rhTSH stimulus. No similar findings were observed in group 2 patients. Moreover, in patients from group 3 (I-131 30 mCi, without L-T4 withdrawal), the outcome of ablation was significantly lower in comparison to patients from group 1 (I-131 30 mCi, with L-T4 withdrawal) in terms of undetectable Tg during the rhTSH stimulus (55.0%, p < 0.001). CONCLUSION rhTSH is highly effective for post-surgical thyroid remnant ablation in low-risk cancer patients using the low 30-mCi dose protocol combined with the short 4-day withdrawal of L-T4. Moreover, in these patients the pre-treatment with furosemide seems to play an important role to further improve the outcome of ablation by reducing the iodine pool.
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Urinary acidification assessed by simultaneous furosemide and fludrocortisone treatment: an alternative to ammonium chloride.
Walsh, SB, Shirley, DG, Wrong, OM, Unwin, RJ
Kidney international. 2007;(12):1310-6
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Abstract
Distal renal tubular acidosis (RTA) can lead to rickets in children or osteomalacia in adults if undetected. This disorder is normally diagnosed by means of an oral ammonium chloride-loading test; however, the procedure often leads to vomiting and abandonment of the test. In this study, we assess an alternative, more palatable approach to test urinary acidification. This was achieved by the simultaneous oral administration of the diuretic furosemide and the mineralocorticoid fludrocortisone to increase distal tubular sodium delivery, principal cell sodium reabsorption, and alpha-intercalated cell proton secretion. We evaluated 11 control subjects and 10 patients with known distal RTA by giving oral ammonium chloride or furosemide/fludrocortisone in random order on separate days. One control and two patients were unable to complete the study owing to vomiting after NH4Cl; however, there were no adverse effects with the furosemide/fludrocortisone treatment. The urine pH decreased to less than 5.3 in the controls with both tests, whereas none of the patients was able to lower the urine pH below 5.3 with either test. We conclude that the simultaneous administration of furosemide and fludrocortisone provides an easy, effective, and well-tolerated alternative to the standard ammonium chloride urinary acidification test for the diagnosis of distal RTA.
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Desmopressin resistant nocturnal polyuria may benefit from furosemide therapy administered in the morning.
De Guchtenaere, A, Vande Walle, C, Van Sintjan, P, Donckerwolcke, R, Raes, A, Dehoorne, J, Van Laecke, E, Hoebeke, P, Vande Walle, J
The Journal of urology. 2007;(6):2635-9; discussion 2639
Abstract
PURPOSE There is increasing evidence that a subgroup of patients with monosymptomatic nocturnal enuresis and nocturnal polyuria resistant to desmopressin may have an abnormal circadian rhythm of renal tubular sodium handling. The pathogenesis of this phenomenon remains to be elucidated. If the increased sodium excretion overnight results in desmopressin resistance, decreasing the sodium excretion overnight may result in subsequently better desmopressin response. MATERIALS AND METHODS We conducted a pilot study of the anti-enuretic and antidiuretic effects of desmopressin combined with 0.5 mg/kg furosemide daily in patients with desmopressin resistant nocturnal polyuria despite dietary sodium and protein restriction. Values were plotted against the reference frame of a desmopressin responsive enuresis group. RESULTS Baseline values revealed significantly lower urinary osmolality and higher diuresis rate overnight compared to the reference population (monosymptomatic nocturnal enuresis desmopressin responders). Introduction of desmopressin resulted in normalization of nocturnal urinary osmolality. However, nocturnal polyuria persisted, despite reaching maximal urinary concentration overnight. Although protein and sodium restriction resulted in a significant decrease in urinary osmolality and diuresis rate, the difference was not clinically important enough to reach normal values or to achieve continence. Furosemide in the morning resulted in a significant increase in diuresis and osmotic and sodium excretion during the day, and decreased nighttime diuresis and osmotic excretion. In 9 of 12 patients the nocturnal antidiuretic effect resulted in an anti-enuretic effect, defined as enuresis less than 1 wet night per month. In 3 patients insufficient anti-enuretic effects were obtained despite significant antidiuresis. CONCLUSIONS This pilot study clearly demonstrates that introduction of early morning furosemide results in a significantly lower nocturnal diuresis rate. Reduced diuresis associated with unchanged urinary osmolality results in decreased nocturnal osmotic excretion in compensation for increased osmotic (sodium) excretion during the daytime.
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Effects of diuretics on iodine uptake in non-toxic goitre: comparison with low-iodine diet.
Kapucu, LO, Azizoglu, F, Ayvaz, G, Karakoc, A
European journal of nuclear medicine and molecular imaging. 2003;(9):1270-2
Abstract
Low-iodine diet has been employed to achieve iodine depletion prior to radioiodine (RI) therapy. However, treatment with diuretics may be more effective than low-iodine diet in causing iodine depletion and subsequent increase in RI uptake by the thyroid. Fifty-five patients with non-toxic goitre were given 0.20 MBq RI p.o. on the first day of the study and thyroid uptake was measured. In 15 patients, a low-iodine diet was started and continued for 14 days. The remaining 40 patients received furosemide 40 mg/day orally for 5 days with an unrestricted diet. On the 15th day of the study, all patients were given 0.20 MBq RI p.o. and thyroid RI uptake was measured again. Additionally, 24-h urinary iodine excretion and RI clearance were measured on the 1st and 6th days in 21 patients from the furosemide group and on the 1st and 15th days in eight patients from the diet group. Furosemide administration led to a 58.40% increase in iodine uptake over the baseline value, which was significantly higher than the increase caused by low-iodine diet (17.22%) ( P<0.0001). Urinary excretion of RI decreased in both groups similarly (furosemide, 29.45%; low-iodine diet, 21.06%; P=0.33). Iodine clearance also decreased in each group similarly (10.61% vs 7.53%, P=0.53). Treatment with furosemide prior to administration of RI increases the uptake of RI by the thyroid more effectively than does low-iodine diet.
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Reduction of oxidative stress augments natriuretic effect of furosemide in moderate heart failure.
Tomiyama, H, Watanabe, G, Yoshida, H, Doba, N, Yamashina, A
American heart journal. 2003;(1):E2
Abstract
BACKGROUND The significance of antioxidant therapy in heart failure has not been fully examined. This study evaluated whether vitamin C has beneficial effects on renal function or augments the renal effects of furosemide in patients with heart failure. METHODS There were 2 protocols. In protocol 1, plasma level of thiobarbituric acid-reactive substances (TBARS) and renal function were assessed before and after intravenous infusion of vitamin C or placebo in 8 patients with moderate congestive heart failure (CHF) treated with enalapril. In protocol 2, a randomized crossover study was performed in patients with moderate CHF treated with either an ACE inhibitor (enalapril) (n = 10) or an angiotensin II receptor antagonist (losartan) (n = 9) and in asymptomatic patients with impaired left ventricular function treated with enalapril (n = 8). TBARS and renal function were assessed before and after intravenous infusion of furosemide alone, coinfusion of furosemide with placebo and vitamin C, or coinfusion of furosemide with vitamin C and a kallikrein inhibitor (nafamostat mesilate). RESULTS In protocol 1, although vitamin C reduced TBARS, it did not affect renal function. In protocol 2, TBARS was higher in patients with moderate CHF than in asymptomatic patients. Vitamin C augmented natriuretic effect of furosemide (from 179 +/- 98 to 192 +/- 104 micromol/min, P <.01) only in patients with moderate CHF treated with enalapril but not in the other 2 groups. Nafamostat mesilate prevented this augmentation. CONCLUSIONS In patients with CHF treated with enalapril, counteraction of the increased oxidative stress by vitamin C may contribute to the augmented natriuretic effect of furosemide through the renal kinin-nitric oxide pathway.