-
1.
Controlled Delivery of 80 mg Aerosol Furosemide Does Not Achieve Consistent Dyspnea Relief in Patients.
Hallowell, RW, Schwartzstein, R, O'Donnell, CR, Sheridan, A, Banzett, RB
Lung. 2020;(1):113-120
-
-
Free full text
-
Abstract
PURPOSE Aerosol furosemide may be an option to treat refractory dyspnea, though doses, methods of delivery, and outcomes have been variable. We hypothesized that controlled delivery of high dose aerosol furosemide would reduce variability of dyspnea relief in patients with underlying pulmonary disease. METHODS Seventeen patients with chronic exertional dyspnea were recruited. Patients rated recently recalled breathing discomfort on a numerical rating scale (NRS) and the multidimensional dyspnea profile (MDP). They then performed graded exercise using an arm-ergometer. The NRS was completed following each exercise grade, and the MDP was repeated after a pre-defined dyspnea threshold was reached. During separate visits, patients received either aerosol saline or 80 mg of aerosol furosemide in a randomized, double-blind, crossover design. After treatment, graded exercise to the pre-treatment level was repeated, followed by completion of the NRS and MDP. Treatment effect was defined as the difference between pre- and post-treatment NRS at end exercise, expressed in absolute terms as % Full Scale. "Responders" were defined as those showing treatment effect ≥ 20% of full scale. RESULTS Final analysis included 15 patients. Neither treatment produced a statistically significant change in NRS and there was no significant difference between treatments (p = 0.45). There were four "responders" and one patient whose dyspnea worsened with furosemide; two patients were responders with saline, of whom one also responded to furosemide. No adverse events were reported. CONCLUSIONS High dose controlled delivery aerosol furosemide was not statistically different from saline placebo at reducing exercise-induced dyspnea. However, a clinically meaningful improvement was noted in some patients.
-
2.
Higher Diuretic Requirements in Acute Heart Failure With Admission Hyponatraemia Versus Normonatraemia.
Omar, HR, Guglin, M
Heart, lung & circulation. 2020;(2):233-241
Abstract
BACKGROUND Diuretic requirements in patients with acute decompensated heart failure (ADHF) and hyponatraemia versus normonatraemia on admission has not been previously explored. METHODS The Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial dataset was utilised to examine the characteristics and diuretic requirements of patients with ADHF with hyponatraemia or normonatraemia on admission. RESULTS Patients with ADHF and admission hyponatraemia (n = 103, average Na 130.2 meq/L) had a higher degree of congestion evident in higher frequency of jugular venous distension (JVD) >12 cmH2O (p = 0.007), 2+ lower extremity oedema (p = 0.001), and higher right atrial pressure (p = 0.007), compared with normonatraemic patients (n = 327, average Na 138.6 meq/L). Despite a similar baseline furosemide dose in both groups (median 200 mg), the hyponatraemia group received higher in-hospital furosemide (280 vs. 200 mg, in both groups, respectively, p < 0.001) which represented a higher percentage of furosemide utilisation relative to baseline, compared with the normonatraemia group (33% vs 0%, in both groups respectively, p = 0.007). With in-hospital diuresis, the Na level of hyponatraemic subjects started significantly increasing at discharge and up to 6 months after randomisation-all relative to baseline. Hyponatraemic patients had significantly lower systolic blood pressure (SBP) longitudinally at multiple time points compared with normonataremic patients, but it did not further decrease despite the higher furosemide dose in the former group. CONCLUSION Patients with ADHF and hyponatraemia on admission had a higher degree of congestion and required higher doses of furosemide, compared with normonatraemic subjects. The lower Na and SBP in this instance should not lead to withholding or minimising diuretic dosage which should rather be dictated by volume status.
-
3.
Acute kidney injury.
Reis, T
Revista da Associacao Medica Brasileira (1992). 2020;(Suppl 1):s68-s74
-
4.
CA125-Guided Diuretic Treatment Versus Usual Care in Patients With Acute Heart Failure and Renal Dysfunction.
Núñez, J, Llàcer, P, García-Blas, S, Bonanad, C, Ventura, S, Núñez, JM, Sánchez, R, Fácila, L, de la Espriella, R, Vaquer, JM, et al
The American journal of medicine. 2020;(3):370-380.e4
Abstract
BACKGROUND The optimal diuretic treatment strategy for patients with acute heart failure and renal dysfunction remains unclear. Plasma carbohydrate antigen 125 (CA125) is a surrogate of fluid overload and a potentially valuable tool for guiding decongestion therapy. The aim of this study was to determine if a CA125-guided diuretic strategy is superior to usual care in terms of short-term renal function in patients with acute heart failure and renal dysfunction at presentation. METHODS This multicenter, open-label study randomized 160 patients with acute heart failure and renal dysfunction into 2 groups (1:1). Loop diuretics doses were established according to CA125 levels in the CA125-guided group (n = 79) and in clinical evaluation in the usual-care group (n = 81). Changes in estimated glomerular filtration rate (eGFR) at 72 and 24 hours were the co-primary endpoints, respectively. RESULTS The mean age was 78 ± 8 years, the median amino-terminal pro-brain natriuretic peptide was 7765 pg/mL, and the mean eGFR was 33.7 ± 11.3 mL/min/1.73m2. Over 72 hours, the CA125-guided group received higher furosemide equivalent dose compared to usual care (P = 0.011), which translated into higher urine volume (P = 0.042). Moreover, patients in the active arm with CA125 >35 U/mL received the highest furosemide equivalent dose (P <0.001) and had higher diuresis (P = 0.013). At 72 hours, eGFR (mL/min/1.73m2) significantly improved in the CA125-guided group (37.5 vs 34.8, P = 0.036), with no significant changes at 24 hours (35.8 vs 39.5, P = 0.391). CONCLUSION A CA125-guided diuretic strategy significantly improved eGFR and other renal function parameters at 72 hours in patients with acute heart failure and renal dysfunction.
-
5.
Meta-Analysis Comparing Torsemide Versus Furosemide in Patients With Heart Failure.
Abraham, B, Megaly, M, Sous, M, Fransawyalkomos, M, Saad, M, Fraser, R, Topf, J, Goldsmith, S, Simegn, M, Bart, B, et al
The American journal of cardiology. 2020;(1):92-99
Abstract
Although torsemide's oral bioavailability and half-life theoretically render it a more efficient diuretic than furosemide, the clinical outcomes of torsemide compared with furosemide remain unclear. We performed a systematic review and meta-analysis, including all published studies that compared torsemide and furosemide use in heart failure patients from January 1996 through August 2019. Nineteen studies (9 randomized control trials [RCTs] and 10 observational studies) with a total of 19,280 patients were included. During a mean follow-up duration of 15 months, torsemide was associated with a numerically lower risk of hospitalization due to heart failure (10.6% vs 18.4%; odds ratio [OR] 0.72, 95% confidence interval [CI] [0.51, 1.03], p = 0.07, I2 = 18%; number needed to treat [NNT] = 23) compared with furosemide. Torsemide was associated with statistically significant more improvement in functional status from New York Heart Association (NYHA) class III/IV to I/II (72.5% vs 58%; OR 2.32, 95% CI (1.32, 4.1), p = 0.004, I2 = 27%; NNT = 5) and lower risk of cardiac mortality (1.5% vs 4.4%; OR 0.37, 95% CI (0.20, 0.66), p <0.001, I2 = 0%, NNT = 40) compared with furosemide. However, there was no difference in all-cause mortality or medication side effects between the 2 groups. In conclusion, compared with furosemide, torsemide use was associated with significant more improvement in functional status and lower cardiac mortality; and numerically fewer hospitalizations in patients with heart failure.
-
6.
Chronic kidney disease progression in patients with resistant hypertension subject to 2 therapeutic strategies: Intensification with loop diuretics vs aldosterone antagonists.
Verdalles, U, Goicoechea, M, García de Vinuesa, S, Torres, E, Hernández, A, Verde, E, Pérez de José, A, Luño, J
Nefrologia. 2020;(1):65-73
Abstract
INTRODUCTION Actualy, there are few data about glomerular filtration rate (eGFR) drop in patients with resistant hypertension and how diferent therapies can modify chronic kidney disease progression (CKD). OBJECTIVE To evaluate CKD progression in patients with resistant hypertension undergoing 2diferent therapies: treatment with spironolactone or furosemide. METHODS We included 30 patients (21M, 9W) with a mean age of 66.3±9.1 years, eGFR 55.8±16.5ml/min/1.73 m2, SBP 162.8±8.2 and DBP 90.2±6.2mmHg: 15 patients received spironolactone and 15 furosemide and we followed up them a median of 32 months (28-41). RESULTS The mean annual eGFR decrease was -2.8±5.4ml/min/1.73 m2. In spironolactone group was -2.1±4.8ml/min/1.73 m2 and in furosemide group was -3.2±5.6ml/min/1.73 m2, P<0.01. In patients received spironolactone, SBP decreased 23±9mmHg and in furosemide group decreased 16±3mmHg, P<.01. DBP decreased 10±8mmHg and 6±2mmHg, respectively (P<.01). Treatment with spironolactone reduced albuminuria from a serum albumin/creatine ratio of 210 (121-385) mg/g to 65 (45-120) mg/g at the end of follow-up, P<.01. There were no significant changes in the albumin/creatinine ratio in the furosemide group. The slower drop in kidney function was associated with lower SBP (P=.04), higher GFR (P=.01), lower albuminuria (P=.01), not diabetes mellitus (P=.01) and treatment with spironolactone (P=.02). Treatment with spironolactone (OR 2.13, IC 1.89-2.29) and lower albuminuria (OR 0.98, CI 0.97-0.99) maintain their independent predictive power in a multivariate model. CONCLUSION Treatment with spironolactone is more effective reducing BP and albuminuria in patients with resistant hypertension compared with furosemide and it is associated with a slower progression of CKD in the long term follow up.
-
7.
Efficacy of Furosemide, Oral Sodium Chloride, and Fluid Restriction for Treatment of Syndrome of Inappropriate Antidiuresis (SIAD): An Open-label Randomized Controlled Study (The EFFUSE-FLUID Trial).
Krisanapan, P, Vongsanim, S, Pin-On, P, Ruengorn, C, Noppakun, K
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2020;(2):203-212
Abstract
RATIONALE & OBJECTIVE First-line therapy for syndrome of inappropriate antidiuresis (SIAD) is fluid restriction. Additional treatment for patients who do not respond to fluid restriction are water restriction with furosemide or water restriction with furosemide and salt supplementation. However, the efficacy of these treatments has never been tested in a randomized controlled study. The objective of this study was to investigate whether, combined with fluid restriction, furosemide with or without sodium chloride (NaCl) supplementation was more effective than fluid restriction alone in the treatment of hyponatremia in SIAD. STUDY DESIGN Open-label randomized controlled study. SETTING & PARTICIPANTS Patients with serum sodium concentrations ([Na+]) ≤ 130mmol/L due to SIAD. INTERVENTION(S): Random assignment to 1 of 3 groups: fluid restriction alone (FR), fluid restriction and furosemide (FR+FM), or fluid restriction, furosemide, and NaCl (FR+FM+NaCl). Strictness of fluid restriction (<1,000 or<500mL/d) was guided by the urine to serum electrolyte ratio. Furosemide dosage was 20 to 40mg/d. NaCl supplements were 3g/d. All treatments were continued for 28 days. OUTCOMES The primary outcome was change in [Na+] at days 4, 7, 14, and 28 after randomization. RESULTS 92 patients were recruited (FR, n=31; FR+FM, n=30; FR+FM+NaCl, n=31). Baseline [Na+] was 125±4mmol/L, and there were no significant differences between groups. Mean [Na+] on day 4 in all treatment groups was significantly increased from baseline by 5mmol/L (P<0.001); however, the change in [Na+] was not significantly different across groups (P=0.7). There was no significant difference in percentage of patients or time to reach [Na+] ≥ 130 or≥135mmol/L across the 3 groups. Acute kidney injury and hypokalemia (potassium≤3.0mmol/L) were more common in patients receiving furosemide. LIMITATIONS Open-label treatment. CONCLUSIONS In patients with SIAD, furosemide with NaCl supplement in combination with fluid restriction did not show benefits in correction of [Na+] compared with treatment with fluid restriction alone. Incidences of acute kidney injury and hypokalemia were increased in patients receiving furosemide. FUNDING None. TRIAL REGISTRATION Registered at the Thai Clinical Trial Registry with study number TCTR20170629004.
-
8.
Diuretic Strategies for Loop Diuretic Resistance in Acute Heart Failure: The 3T Trial.
Cox, ZL, Hung, R, Lenihan, DJ, Testani, JM
JACC. Heart failure. 2020;(3):157-168
Abstract
OBJECTIVES This study compared combination diuretic strategies in acute heart failure (AHF) complicated by diuretic resistance (DR). BACKGROUND Combination diuretic regimens to overcome loop DR are commonly used but with limited evidence. METHODS This study was a randomized, double-blinded trial in 60 patients hospitalized with AHF and intravenous (IV) loop DR. Patients were randomized to oral metolazone, IV chlorothiazide, or tolvaptan therapy. All patients received concomitant high-dose IV infusions of furosemide. The primary outcome was 48-h weight loss. RESULTS The cohort exhibited DR prior to enrollment, producing 1,188 ± 476 ml of urine in 12 h during high-dose loop diuretic therapy (IV furosemide: 612 ± 439 mg/day). All 3 interventions significantly improved diuretic efficacy (p < 0.001). Compared to metolazone (4.6 ± 2.7 kg), neither IV chlorothiazide (5.8 ± 2.7 kg; 1.2 kg [95% confidence interval (CI)]: -2.9 to 0.6; p = 0.292) nor tolvaptan (4.1 ± 3.3 kg; 0.5 kg [95% CI: -1.5 to 2.4; p = 0.456) resulted in more weight loss at 48 h. Median (interquartile range [IQR]) cumulative urine output increased significantly and did not differ among those receiving metolazone (7.78 [IQR: 6.59 to 10.10] l) and chlorothiazide (8.77 [IQR: 7.37 to 10.86] l; p = 0.245) or tolvaptan (9.70 [IQR: 6.36 to 13.81] l; p = 0.160). Serum sodium decreased less with tolvaptan than with metolazone (+4 ± 5 vs. -1 ± 3 mEq/l; p = 0.001), but 48-h spot urine sodium was lower with tolvaptan (58 ± 25 mmol/l) than with metolazone (104 ± 16 mmol/l; p = 0.002) and with chlorothiazide (117 ± 14 mmol/l; p < 0.001). CONCLUSIONS In this moderately sized DR trial, weight loss was excellent with the addition of metolazone, IV chlorothiazide, or tolvaptan to loop diuretics, without a detectable between-group difference. (Comparison of Oral or Intravenous Thiazides vs. tolvaptan in Diuretic Resistant Decompensated Heart Failure [3T]; NCT02606253).
-
9.
Heart failure in the outpatient versus inpatient setting: findings from the BIOSTAT-CHF study.
Ferreira, JP, Metra, M, Mordi, I, Gregson, J, Ter Maaten, JM, Tromp, J, Anker, SD, Dickstein, K, Hillege, HL, Ng, LL, et al
European journal of heart failure. 2019;(1):112-120
Abstract
INTRODUCTION Patients with symptomatic heart failure (HF) require additive therapies and have a poor prognosis. However, patient characteristics and clinical outcome between HF patients treated in the outpatient setting vs. those who are hospitalized remain scarce. METHODS AND RESULTS The BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) included 2516 patients with symptoms and/or signs of HF: 1694 as inpatients and 822 as outpatients. Compared to ambulatory HF patients, inpatients had higher heart rate, urea, N-terminal pro-brain natriuretic peptide, lower blood pressure, lower estimated glomerular filtration rate, sodium, potassium, high-density lipoprotein cholesterol, had more often peripheral oedema, diabetes, anaemia, and were less often treated with beta-blockers and angiotensin-converting enzyme inhibitors (ACEi). Outpatients had a more frequent history of HF hospitalization and received more frequently beta-blockers and/or ACEi/angiotensin receptor blockers up-titrated to target doses (P < 0.001). Inpatients had higher rates of the primary outcome of death or HF hospitalization: incidence rate per 100 person-years of 33.4 [95% confidence interval (CI) 31.1-35.9] for inpatients vs. 18.5 (95% CI 16.4-21.0) for outpatients; adjusted hazard ratio 1.24 (95% CI 1.07-1.43). Subdividing patients into low, intermediate and high-risk categories, the primary outcome event rates were 14.3 (95% CI 12.3-16.7), 36.6 (95% CI 32.2-41.5), and 71.3 (95% CI 64.4-79.0) for inpatients vs. 8.4 (95% CI 6.6-10.6), 29.8 (95% CI 24.5-36.2), and 43.3 (95% CI 34.7-54.0) for outpatients, respectively. These findings were externally replicated. CONCLUSIONS Marked differences were observed between inpatients and outpatients with HF. Overall, inpatients were sicker and had higher event rates. However, a substantial proportion of outpatients had similar or higher event rates compared to inpatients. These findings suggest that HF outpatients also have poor prognosis and may be the focus of future trials.
-
10.
Serial assessment of spot urine sodium predicts effectiveness of decongestion and outcome in patients with acute heart failure.
Biegus, J, Zymliński, R, Sokolski, M, Todd, J, Cotter, G, Metra, M, Jankowska, EA, Banasiak, W, Ponikowski, P
European journal of heart failure. 2019;(5):624-633
Abstract
AIMS: The clinical significance of the measurement of urine sodium concentration (UNa+ ) in response to loop diuretic administration in patients with acute heart failure (AHF) is still unsettled. We studied the association of serial measurements of spot UNa+ during the first 48 h of AHF treatment with the indices of decongestion, renal function, and prognosis. METHODS AND RESULTS We enrolled 111 AHF patients, all of whom received intravenous furosemide on admission. The mean spot UNa+ significantly increased in the 6 h sample (P < 0.05 vs. baseline) and returned to baseline values in the 24 and 48 h samples. Based on the increase or decrease/no change of UNa+ in the 6 and 48 h samples vs. baseline, patients were divided into two groups at each time point, respectively. Patients did not differ in baseline clinical and laboratory characteristics. Patients with a decrease/no change of UNa+ in the 6 and 48 h samples had a lower weight loss during hospitalization. Patients with a decrease/no change of UNa+ in the 48 h sample had a poorer diuretic response and a significant increase in the urinary levels of the tubular biomarkers: kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin. Low UNa+ and decrease/no change in UNa+ in the 6 and 48 h samples were independent predictors of higher risk of all-cause mortality during 1-year follow-up (all P < 0.05). CONCLUSION In AHF, low spot UNa+ and lack to increase UNa+ in response to intravenous diuretics are associated with poor diuretic response, markers of tubular injury and high risk of 1-year mortality.