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Comparative effectiveness of furosemide vs torasemide in symptomatic therapy in heart failure patients: A randomized controlled study protocol.
Li, Y, Li, L, Guo, Z, Zhang, S
Medicine. 2021;(7):e24661
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Abstract
BACKGROUND We performed this randomized controlled study protocol to investigate the efficacy and adverse effects of furosemide vs torasemide in patients with heart failure (HF). METHOD The present study was authorized by the local research ethics committee of Shanxi Cardiovascular Hospital (no. 48736645) and informed consent was obtained from all patients. Patients were enrolled in a consecutive prospective manner on a voluntary basis. Patients who were aged 18 years and older with HF who were eligible to enroll in this randomized trial. All patients had evidence of left ventricular systolic dysfunction, confirmed by echocardiographic or nuclear imaging. The exclusion criteria were left ventricular diastolic dysfunction only, or receipt of medical or pharmaceutical care in other health systems. The primary efficacy end point was the change in procollagen type I carboxyterminal peptide (PICP) serum levels between baseline and final visit. Secondary efficacy variables included parameters related to the clinical course of HF, such as body weight, presence of edema, signs and symptoms of HF, electrocardiogram and echocardiographic evaluation, amino-terminal pro brain-type natriuretic peptide (NT-proBNP) serum levels measured by ELISA method, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate, and renal function. RESULTS One hundred patients who met the inclusion criteria were included in our study, Table 1 showed the effects of furosemide and torsemide on measures of clinical outcomes. DISCUSSION Fluid overload is the primary cause of hospitalization among patients with HF. Preventing circulatory congestion requires careful control of dietary sodium and chronic administration of loop diuretics. Torasemide and furosemide are representatives of loop diuretics with an identical diuretic mechanism, but different pharmacokinetic properties and additional effects. There is a need for reliable conclusion regarding the comparison of furosemide and torasemide in patients with HF. Several limitation should be noted: 1. the small number of participants did not enable assessment of the impact of torasemide and furosemide in different clinically relevant subgroups that is, elderly, patients with chronic kidney disease, dilated cardiomyopathy; 2. short-term follow up might lead to underestimation of the complications; 3. methodological weakness in study design may affect the results. Future high quality studies were still required.
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Randomized study comparing mannitol with furosemide for the prevention of cisplatin-induced renal toxicity in non-small cell lung cancer: The OLCSG1406 trial.
Makimoto, G, Hotta, K, Oze, I, Ninomiya, K, Nakanishi, M, Hara, N, Kano, H, Watanabe, H, Hata, Y, Nishii, K, et al
Asia-Pacific journal of clinical oncology. 2021;(1):101-108
Abstract
AIM: Evidence is lacking on the best standard method for forced diuresis to prevent cisplatin-induced nephrotoxicity. We compared the cisplatin-induced nephrotoxicity prevention effect of furosemide or mannitol in patients with advanced non-small cell lung cancer. METHODS Patients with advanced non-small cell lung cancer suitable to receive cisplatin-containing regimen were randomly assigned to receive furosemide or mannitol with appropriate hydration. The primary endpoint was the proportion of ≥ grade 1 serum creatinine elevation in the first cycle. RESULTS The trial was terminated early with 44 (22 per arm) of the planned 66 patients because of slow accrual. Patients' characteristics were well balanced with median baseline creatinine clearance of 98.0 and 95.1 mL/min in the furosemide and mannitol arms, respectively. In the first cycle, two (9%) and four (18%) patients developed grade 1 creatinine elevation (P = .66), respectively, despite no ≥ grade 2 toxicity. The median times to develop the worst creatinine score were 10 and 8 days, respectively. For all cycles, median times to recover to grade 0 were 56 and 20 days, respectively. The furosemide arm was characterized by relatively high urine output after cisplatin administration (900 vs 550 mL/h), low frequency of unplanned additional hydration (14% vs 32%), and high incidence of hyponatremia (18% and 5%) compared with the mannitol arm. Both arms showed similar progression-free survival and overall survival. CONCLUSION The preventive effect of the two forced diuretics on cisplatin-induced nephrotoxicity was not significantly different. However, the two diuretics have some distinct types of clinical presentations.
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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.
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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.
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Randomized Phase II Study Comparing Mannitol with Furosemide for the Prevention of Renal Toxicity Induced by Cisplatin-based Chemotherapy with Short-term Low-volume Hydration in Advanced Non-small Cell Lung Cancer: The OLCSG1406 Study Protocol.
Makimoto, G, Ichihara, E, Hotta, K, Ninomiya, K, Oze, I, Minami, D, Ninomiya, T, Kubo, T, Ohashi, K, Tabata, M, et al
Acta medica Okayama. 2018;(3):319-323
Abstract
Although cisplatin-based chemotherapy shows a survival advantage compared to carboplatin for treating advanced non-small cell lung cancer, high-volume hydration and a long infusion time are necessary to avoid nephrotoxicity, and cisplatin-based chemotherapy has been difficult to administer in outpatient settings. A low-volume hydration method using mannitol or furosemide as forced diuresis was recently introduced, but there are no clear conclusions regarding which agent should be used. We describe our ongoing randomized phase II trial (the OLCSG1406 Study) evaluating the efficacy of forced diuresis. This study will clarify whether mannitol or furosemide is more suitable in cisplatin-based chemotherapy with low-volume hydration.
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Inhaled furosemide for relief of air hunger versus sense of breathing effort: a randomized controlled trial.
Grogono, JC, Butler, C, Izadi, H, Moosavi, SH
Respiratory research. 2018;(1):181
Abstract
BACKGROUND Inhaled furosemide offers a potentially novel treatment for dyspnoea, which may reflect modulation of pulmonary stretch receptor feedback to the brain. Specificity of relief is unclear because different neural pathways may account for different components of clinical dyspnoea. Our objective was to evaluate if inhaled furosemide relieves the air hunger component (uncomfortable urge to breathe) but not the sense of breathing work/effort of dyspnoea. METHODS A randomised, double blind, placebo-controlled crossover trial in 16 healthy volunteers studied in a university research laboratory. Each participant received 3 mist inhalations (either 40 mg furosemide or 4 ml saline) separated by 30-60 min on 2 test days. Each participant was randomised to mist order 'furosemide-saline-furosemide' (n- = 8) or 'saline-furosemide-saline' (n = 8) on both days. One day involved hypercapnic air hunger tests (mean ± SD PCO2 = 50 ± 3.7 mmHg; constrained ventilation = 9 ± 1.5 L/min), the other involved work/effort tests with targeted ventilation (17 ± 3.1 L/min) and external resistive load (20cmH2O/L/s). Primary outcome was ratings of air hunger or work/effort every 15 s on a visual analogue scale. During saline inhalations, 1.5 mg furosemide was infused intravenously to match the expected systemic absorption from the lungs when furosemide is inhaled. Corresponding infusions of saline during furosemide inhalations maintained procedural blinding. Average visual analogue scale ratings (%full scale) during the last minute of air hunger or work/effort stimuli were analysed using Linear Mixed Methods. RESULTS Data from all 16 participants were analysed. Inhaled furosemide relative to inhaled saline significantly improved visual analogues scale ratings of air hunger (Least Squares Mean ± SE - 9.7 ± 2%; p = 0.0015) but not work/effort (+ 1.6 ± 2%; p = 0.903). There were no significant adverse events. CONCLUSIONS Inhaled furosemide was effective at relieving laboratory induced air hunger but not work/effort in healthy adults; this is consistent with the notion that modulation of pulmonary stretch receptor feedback by inhaled furosemide leads to dyspnoea relief that is specific to air hunger, the most unpleasant quality of dyspnoea. FUNDING Oxford Brookes University Central Research Fund. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02881866 . Retrospectively registered on 29th August 2018.
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Bolus Injection Versus Infusion of Furosemide in Kidney Transplantation: A Randomized Clinical Trial.
Zomorrodi, A, Mohammadipoor Anvari, H, Kakaei, F, Solymanzadeh, F, Khanlari, E, Bagheri, A
Urology journal. 2017;(2):3013-3017
Abstract
PURPOSE Furosemide is commonly administered to increase the urinary output in patients with transplanted kidneys. This study compared the two administration routes of furosemide (bolus versus infusion) in kidney transplanted patients. MATERIALS AND METHODS Fifty patients who had undergone kidney transplantation in 2015 in a hospital in Tabriz, Iran, were included in this clinical trial. They were divided into two groups: bolus (120 mg stat) and infusion (4 mg/minute) groups. The primary outcome was urine onset time. Secondary outcomes were urine output volume, vital signs (blood pressure, heart rate), and electrolyte level (creatinine, blood urea nitrogen, sodium and potassium). After arterial and venous anastomoses, arterial clamp removal time and diuresis onset were recorded. Finally, theurinary output volumes of both groups were measured with regular urine bags for an hour after anastomosis. Then it was repeated each three hours for 24 hours, and eventually two and three days thereafter. Finally, all data were statistically analyzed. RESULTS Around 72% of the patients were men (mean age of 37.15 ± 14.67 years). Urine output was higher in bolus group but it was not statistically significant. Diuresis duration was measured after arterial declamping and its averages were 5.41 ± 3.7 minutes and 9.36 ± 7.65 minutes in bolus and infusion groups, respectively (P = .040). Furosemide bolus injection and infusion had no significant effect on creatinine, blood urea nitrogen, sodium and potassium. CONCLUSION Furosemide bolus injection can reduce diuresis onset time compared to furosemide infusion.
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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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Dominance of furosemide for loop diuretic therapy in heart failure: time to revisit the alternatives?
Bikdeli, B, Strait, KM, Dharmarajan, K, Partovian, C, Coca, SG, Kim, N, Li, SX, Testani, JM, Khan, U, Krumholz, HM
Journal of the American College of Cardiology. 2013;(14):1549-50
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Continuous infusion versus intermittent bolus furosemide in ADHF: an updated meta-analysis of randomized control trials.
Amer, M, Adomaityte, J, Qayyum, R
Journal of hospital medicine. 2012;(3):270-5
Abstract
OBJECTIVE Administering intermittent boluses of furosemide to patients with acute decompensated heart failure (ADHF) often leads to unfavorable hemodynamic changes. Continuous infusion may induce similar or greater diuresis without adverse hemodynamic consequences. We conducted a systemic review and meta-analysis of randomized clinical trials that compared the effects of continuous infusion and intermittent bolus of furosemide in patients hospitalized with ADHF. METHODS We searched PubMed, EMBASE, and The Cochrane Central Register of Controlled Trials databases from their inception until March 2011. Two investigators independently abstracted data on study characteristics, quality, and selected outcomes. Differences between investigators were resolved by mutual consensus. Comparisons were reported as the weighted mean difference (WMDs). RESULTS Ten trials involving a total of 564 patients were included. When administered as a continuous infusion, furosemide resulted in greater diuresis (WMD, -240.54 mL/24 hours/100 mg furosemide; 95% confidence interval [CI], -462.42 to -18.66) and reduction in total body weight (WMD, -0.78 kg; 95% CI, -1.54 to -0.03), than when administered in intermittent boluses. Urinary sodium excretion (WMD, -20.26 mmol/24 hours; 95% CI, -60.48 to 19.96) and duration of hospital stay (WMD, 0.99 days; 95% CI, -2.08 to 4.06) were not different between the 2 groups. CONCLUSION This meta-analysis showed statistical support for administering furosemide as a continuous infusion for greater diuresis and reduction in total body weight in patients hospitalized with ADHF. With the exception of greater diuresis, available data are homogenous for the reported outcomes but lack information on clinical endpoints. Larger studies are needed to provide robust recommendations for clinical practice.