Furosemide Equivalent Dose Research Articles

Effects of Very Low (12/13mg) and Low Dose (24/26mg) Sacubitril/Valsartan on N-Terminal Pro-B-Type Natriuretic Peptide

Introduction Sacubitril/valsartan (S/V) has been shown to decrease N-terminal pro-B-type natriuretic peptide (NT-pro BNP) levels. Reduction of NT-proBNP is associated with lower morbidity and mortality rates. However, there is very little data with the effects of low dose S/V on NT-proBNP. Methodology This was a retrospective study conducted between October 2015 and January 2018 of patients who received either low dose or very low dose S/V. Patients were divided into 3 groups based on S/V dosing. Group 1 patients received very low dose, group 2 patients received very low dose titrated to low dose, and group 3 patients received low dose. The primary endpoint was the change in NT-proBNP levels between baseline and the most recent obtained value. Results A total of 293 patients were reviewed and 45 patients met inclusion criteria. Across all S/V dosing groups, there was a statistically significant reduction in NT-proBNP levels. The average days of therapy between NT-proBNP values were 108, 149, and 196 in group 1, 2, and 3, respectively. 71% of patients were on loop diuretics prior to S/V with an average furosemide equivalent dose of 73mg which decreased by 27% to 53mg after receiving S/V. Conclusion Low doses of S/V, including half of the lowest dose clinically available, appears to have substantial benefit in terms of NT-proBNP which can be seen within 3 to 6 months. Despite a reduction in loop diuretic dose, there was still a significant reduction in NT-proBNP which may be attributed to the natriuretic effect of S/V. Although reductions in NT-proBNP levels are associated with improvements in survival, these data cannot be used to infer that a similar reduction in mortality would be expected. However, they do suggest that very low doses of S/V appear to have a biochemical effect and perhaps should be studied in future trials since not all patients can be titrated to the maximum dose of S/V. While patients should be titrated to guideline recommended doses, low doses seem to be beneficial in terms of reducing NT-proBNP levels.

Chronologic Changes and Correlates of Loop Diuretic Dose in Patients with Left Ventricular Assist Device.

No study has systematically evaluated the prevalence and dosages of diuretic use for patients after left ventricular assist device (LVAD) implantation. The primary objective was to characterize chronologic change in prevalence and doses of loop diuretics after LVAD placement. The secondary objective was to identify correlates of actual doses of loop diuretics. We retrospectively reviewed medical records of adult patients with LVAD implantation at the University of Kentucky. Prevalence of diuretic use and furosemide equivalent dose were assessed before LVAD implantation and at seven time points thereafter: 1 week, 1 month, 3 months, 6 months, 1 year, 18 months, and 2 years. Correlation analyses and linear mixed modeling were used to identify correlates of diuretic dose before and after LVAD implantation. Eighty-two consecutive eligible patients were reviewed. The prevalence of loop diuretic use was 95% at baseline but significantly lower than that at all subsequent time points (p < 0.048 for all). Nevertheless, more than half of patients on whom we had such follow-up data were on loop diuretics 2 years after LVAD implantation. Average furosemide equivalent dose was significantly lower at every time point after implantation compared with baseline (p < 0.006 for all). Blood urine nitrogen (BUN) was the most robust predictor of dose after LVAD implant. The prevalence and average furosemide equivalent dose were significantly reduced after LVAD implantation, but the use of loop diuretic remained more than 50% for up to 2 years. Consistent association with BUN may indirectly indicate overuse of diuretics post-LVAD implant.

Urine Sodium Content is Highly Variable in Hospitalized Acute Heart Failure Patients: Lasix Urine is Not Necessarily “Half-Normal Saline”

Background: Decongestion is the primary therapeutic objective in hospitalized acute heart failure (AHF) patients. The major driver of volume overload is sodium retention, and therapeutic approaches, such as loop diuretics, target elimination of sodium with water passively following. However, sodium output is rarely directly monitored in these patients, and natriuresis is inferred from parameters such as urine output. Common teaching holds that the sodium concentration of loop diuretic-induced urine is approximately “half-normal saline” (77 mmol/L NaCl). However, this approximation has not been rigorously tested in contemporary AHF patients. Hypothesis: Contrary to traditional wisdom, urine from hospitalized AHF patients receiving loop diuretics will not consistently reflect a sodium content of “half-normal saline.” Methods: Patients in the ROSE-AHF trial were studied. Patients with urine sodium data over 72 hours were analyzed (n = 299). Results: The median furosemide equivalent dose was 559 mg (IQR 300–803) over the 72-hour intervention period. The mean urinary sodium concentration was 56.4 mmol/L ± 21.6 mmol/L, a value significantly lower than the assumed 77 mmol/L (P < .001). There was substantial variability in the sodium content of urine. Sodium content varied within the same patient, as there was only a correlation of r = 0.48 between the first and second 24-hour urine collections (P < .001). Furthermore, on average, there was significant variability in sodium content between patients. Notably, assuming a 77 mmol/L concentration of urine sodium, the 72-hour sodium excretion was overestimated by at least 3 grams in 51.4% and 5 grams by 33.9% of the population. Furthermore, the urine sodium content varied with diuretic response, and patients with greater urine output tended to have higher urine sodium concentration (r = 0.26, P < .001). Remarkably, the total diuretic dose administered inversely correlated with the sodium concentration (r = -0.16, P = .007) and did not correlate with the total sodium output (P = .36). Conclusion: The urinary sodium content of hospitalized HF patients undergoing aggressive diuresis was highly variable between patients and did not consistently reflect “half-normal saline.” Assumption of a fixed sodium content in urine leads to clinically significant over or underestimation of natriuresis. Fig. 1

The independent association between altered renal arterial resistance and loop diuretic dose in chronic heart failure outpatients

BackgroundIn chronic heart failure (CHF) patients there is a wide variability in the minimal effective diuretic dose. The aim of this study is to evaluate whether renal resistance index (RRI) is associated to baseline diuretic dose and the changes at one year. Methods and results250 outpatients in a stable condition and in conventional therapy were enrolled. Baseline RRI was calculated by renal arterial Doppler. The total daily dose of loop diuretics was assessed at baseline and after one year. High diuretic dose (HDD) was defined as a daily furosemide equivalent dose >100mg. RRI was independently associated with baseline HDD at univariate (OR 1.39; 95% CI: 1.233–1.58; p<0.001) and multivariate analysis (OR 1.27; 95% CI: 1.09–1.49; p: 0.002) after correction for other univariate predictors (age, NYHA class, left ventricular ejection fraction, tricuspid annulus peak of systolic excursion, NT-proBNP, glomerular filtration rate by EPI formula and central venous pressure). Moreover, baseline RRI was independently associated to one year stable increase in loop diuretic dose at univariate and multivariate regression analyses. ConclusionsRRI is independently associated with high dose loop diuretics and their increase during a mid-term follow-up thus suggesting its usefulness in detecting an altered diuretic response in CHF outpatients.

Abstract 18301: Neurohormonal Activation Status Influences Prognostic Implication of Diuretics in Acute Decompensated Heart Failure

Introduction: The high serum levels of blood urea nitrogen (BUN) reflects neurohormonal activation including sympathetic nervous system and rennin-angiotensin-aldosterone system in hear failure patients. Although furosemide is a mainstay for acute decompensated heart failure (ADHF) treatment, there is possibility of worsening prognosis by adversely affecting the pathophysiology of ADHF including neurhormonal activation. Hypothesis: We hypothesize that the prognostic implication of furosemide dose is influenced by the degree of neurohormonal activation in ADHF patients. Methods: A total of 1044 patients with ADHF (78.2±12.7 years, 50.8% males) were included retrospectively from 3 hospitals in Japan, and 85 patients (8.1%) died during hospitalization. Patients were divided into 4 groups according to quartiles of total furosemide equivalent dose which was used within 2 days from admission (median 70.0mg, IQR 40-120mg). Patients were also divided to 2 groups according to median serum BUN value of 23 mg/dl (high-BUN group, n=515 and low-BUN group, n=529). Results: In-hospital mortality was increased as furosemide dose was increased (Q1: 8.4%, Q2: 6.0%, Q3: 11.9%, Q4: 18.0%, P=0.009) in high BUN group, but not in the low BUN group (Q1: 2.3%, Q2: 5.6%, Q3: 2.4%, Q4: 6.0%, P=0.28). Moreover, when Q1 group was used as a reference, odds ratio for in-hospital mortality was increased as the dose was increased even after multivariate analysis in high-BUN group (Q2: OR, 0.83; 95% CI, 0.29-2.73; P=0.82, Q3: OR, 1.99; 95% CI, 0.71-5.58; P=0.19, and Q4: OR, 2.84; 95% CI, 1.15-6.99; P=0.02, respectively) but not in low-BUN group (Q2: OR, 1.93; 95% CI, 0.45-8.22; P=0.37, Q3: OR, 1.14; 95% CI, 0.22-6.02; P=0.88, and Q4: OR, 1.85; 95% CI, 0.42-8.20; P=0.42, respectively). Conclusions: High dose furosemide use in ADHF patients increased in-hospital mortality in high-BUN group but not in low-BUN group. This indicates the influence of neurohormonal state on prognostic implication of furosemide dose used in acute phase of ADHF.

Prospective development and validation of a model to predict heart failure hospitalisation

ObjectiveAcute heart failure syndrome (AHFS) is a major cause of hospitalisation and imparts a substantial burden on patients and healthcare systems. Tools to define risk of AHFS hospitalisation are lacking.MethodsA...

The vasopressin V2-receptor antagonist, tolvaptan, can not only induce aquaresis but also enhance natriuresis in heart failure patients refractory to loop diuretics

Purpose: Although experimental studies have demonstrated that tolvaptan (TLV), a selective vasopressin V2-receptor antagonist, induces free water clearance without increasing urine sodium, there are only few reports on its clinical efficacy concerning urodynamics in acute decompensated heart failure (ADHF) patients concomitant with conventional diuretic use in usual practice. Methods: 22 consecutive ADHF patients with volume overload despite using loop diuretics were treated with TLV for 7 days. We divided these patients into two groups, responder (R, ≥+42%) or non-responder (N, <+42%), depending on the median value of urine volume (UV) increase in the first 24h compared with the baseline. Results: UV during the next 24h after TLV treatment was significantly higher than that just before induction of TLV (1701±871ml/day vs. 1137±341 ml/day; P<0.05). Although there was no significant difference in the baseline characteristics including serum creatinine and sodium together with TLV dose (8.8±3.0mg/day vs. 9.5±3.5mg/day, NS) between the groups, the first 24h UV increased and the body weight reduced by Day 7 more in R than in N (108±57% vs. -2±35%, P<0.001; -1.1±1.7kg vs. -0.4±1.1kg, P<0.05, respectively). Despite the decrease in loop diuretics with administration of TLV in both the groups (furosemide equivalent dose: 58±23 to 25±16mg/day in R, 67±63 to 33±22mg/day in N), sodium and potassium excretion in urine in the first 24h was maintained in R but decreased in N (1±34% vs. -47±21%, P<0.001; 8±34 vs. -18±21%, P<0.05, respectively) (Figure). ![Figure][1] Sodium and potassium excretion in urine Conclusions: In some ADHF patients responsive to adjunctive TLV, urinary sodium and potassium excretion is enhanced presumably by the improved efficacy of concomitant use of loop diuretics. [1]: pending:yes

Renal arterial resistance index is independently associate to high diuretic dose in chronic heart failure outpatients

In chronic heart failure (CHF) patients, diuretic administration plays a key role in the control of congestion. However, high diuretic dose (HDD) has been also demonstrated to be associated to a worse prognosis. The aim of this study was to evaluate the factors independently associated to HDD and, in particular, the role of a marker of renal perfusion, the Renal arterial Resistance Index (RRI). We enrolled 250 outpatients (78% males, 64±13 years, NYHA class 2.2±0.6, left ventricular ejection fraction, LVEF, 34±10%) with CHF (ESC criteria) due to left ventricular systolic dysfunction, in stable clinical conditions (> 1 month) and in conventional therapy. All patients underwent: a clinical evaluation to assess NYHA class; a routine chemistry to evaluate NT-proBNP and glomerular filtration rate (GFR) by creatinine (MDRD formula); an echocardiogram to evaluate LVEF and to estimate central venous pressure (CVP); a renal echo-Doppler in order to evaluate RRI. Peak systolic velocity and end diastolic velocity of segmental renal artery was obtained by pulsed Doppler flow and RRI was then calculated. RRI was positively and significantly correlated with furosemide equivalent dose (r: 0.33; p<0.001) and with HDD (r: 0.36; p<0.001). As shown in the table, RRI remained significantly associated with HDD in a multivariate logistic regression analysis including the other factors significantly correlated at univariate analysis.

Differential mortality association of loop diuretic dosage according to blood urea nitrogen and carbohydrate antigen 125 following a hospitalization for acute heart failure

Recent observations in chronic stable heart failure suggest that high-dose loop diuretics (HDLDs) have detrimental prognostic effects in patients with high blood urea nitrogen (BUN), but recent findings have also indicated that diuretics may improve renal function. Carbohydrate antigen 125 (CA125) has been shown to be a surrogate of systemic congestion. We sought to explore whether BUN and CA125 modulate the mortality risk associated with HDLDs following a hospitalization for acute heart failure (AHF). We analysed 1389 consecutive patients discharged for AHF. CA125 and BUN were measured at a mean of 72 ± 12 h after admission. HDLDs (≥120 mg/day in furosemide equivalent dose) were interacted to a four-level variable according to CA125 (>35 U/mL) and BUN (above the median), and related to all-cause mortality. At a median follow-up of 21 months, 561 (40.4%) patients died. The use of HDLDs was independently associated with increased mortality [hazard ratio (HR) 1.23, 95% confidence interval (CI) 1.01-1.50], but this association was not homogeneous across CA125-BUN categories (P for interaction <0.001). In patients with normal CA125, use of HDLDs was associated with high mortality if BUN was above the median (HR 2.29, 95% 1.51-3.46), but not in those with BUN below the median (HR 1.22, 95% CI 0.73-2.04). Conversely, in patients with high CA125, HDLDs showed an association with increased survival if BUN was above the median (HR 0.73, 95% CI 0.55-0.98) but was associated with increased mortality in those with BUN below the median (HR 1.94, 95% CI 1.36-2.76). The risk associated with HDLDs in patients after hospitalization for AHF was dependent on the levels of BUN and CA125. The information provided by these two biomarkers may be helpful in tailoring the dose of loop diuretics at discharge for AHF.