Conventional Diuretics Research Articles

Dynamic changes in serum chloride concentrations during worsening of heart failure and its recovery following conventional diuretic therapy: A single-center study.

Background and aimsFew data are available regarding the dynamic changes in the serum chloride concentrations in heart failure (HF) pathophysiology. The aim of the present study was to investigate changes in the serum chloride concentration under worsening HF and its recovery following conventional diuretic therapy.MethodsBlood test data, including measurements of serum albumin/solutes and b‐type natriuretic peptide, at both worsening and recovery of HF status, were obtained from 47 patients with definite HF.ResultsAmbulatory patients with HF were enrolled and followed up at the outpatient clinic of Nishida Hospital between June 2003 and March 2009. From clinically stable to worsening HF, the serum sodium concentration increased from (mean ± SD) 139 ± 4.1 to 141 ± 5.07 mEq/L (P < 0.05, two‐way analysis of variance) and the serum chloride concentration increased from 101 ± 5.36 to 104 ± 5.44 mEq/L (P < 0.01) among all patients. After resolution of worsening HF by treatment with conventional diuretics, both the serum sodium concentration and serum chloride concentration decreased significantly to 138 ± 5.12 and 99.5 ± 5.33 mEq/L, respectively (P < 0.0001 for each). The absolute changes in the serum sodium concentration from clinically stable HF to worsening HF appeared to be lesser than those in the serum chloride concentration (1.70 ± 4.34 vs 2.72 ± 6.02 mEq/L, P = 0.079, t test), but this was not statistically significant. Absolute changes in the serum sodium concentration from worsening HF to its recovery following treatment with conventional diuretics were lesser than those in the serum chloride concentration (−2.87 ± 4.38 vs −4.45 ± 5.23 mEq/L, P = 0.0068, t test).ConclusionUnder conventional diuretic therapy, greater changes occur in the serum chloride concentration than in the serum sodium concentration under HF state transitions, suggesting that chloride dynamics might contribute more to HF pathophysiology under such therapeutic circumstance.

Effects of tolvaptan on renal function in chronic kidney disease patients with volume overload.

BackgroundFluid overload in chronic kidney disease (CKD) is generally controlled by diuretics, with potentially harmful effects on renal function. The efficacy of tolvaptan, a vasopressin V2-receptor antagonist and aquaretic, has not been evaluated for fluid control in CKD with reduced renal function.MethodsEach patient from a group of 24 CKD patients on tolvaptan 15 mg/d plus conventional diuretics (T group) was matched by age and sex with a patient from a group of 24 CKD patients on conventional nonaquaretic diuretics alone not associated to tolvaptan other than tolvaptan (C group). Changes in renal function were compared between the groups for 1 year.ResultsThere were no significant differences in blood pressure, hemoglobin levels, cardiac function, urine specific gravity, and urinary sodium concentration between the 2 groups at the beginning of the follow-up period and 1 year after. The estimated glomerular filtration rate (eGFR) by the formula developed by Japanese Society of Nephrology (in mL/min/1.73 m2) decreased: C group (from 28.3±13.6 to 23.0±12.3, p=0.09), T group (from 22.7±12.4 to 19.4±12.2, p=0.18), but both did not reach significance. A 50% reduction in eGFR was observed in 4 patients in the C group and 1 in the T group (p<0.05). A subgroup analysis performed on the patients with stage 3–4 CKD demonstrated a significant reduction in eGFR in the C group (n=17, p=0.04), but not in T group (n=17, p=0.07).ConclusionThese results suggest that tolvaptan may have less effects on CKD progression among stage 3–4 CKD patients who are on conventional diuretics.

P277Comparison of changes in the plasma volume and renal function between acetazolamide vs. conventional diuretics: understanding their mechanical differences according to the chloride theory

P277Comparison of changes in the plasma volume and renal function between acetazolamide vs. conventional diuretics: understanding their mechanical differences according to the chloride theory

Survival Benefit of Tolvaptan for Refractory Ascites in Patients with Advanced Cirrhosis

Aims: The study aimed to evaluate the effects of tolvaptan treatment on survival of patients with decompensated liver cirrhosis with refractory ascites. Methods: This multicenter, retrospective, observational study included patients with cirrhosis who were treated with tolvaptan for hepatic ascites refractory to conventional diuretics. Patients who could and could not decrease accompanying diuretics within 1 month after tolvaptan administration were defined as the “Decreased” and “Not-decreased” groups, respectively. Results: Median body weight change 1 week after tolvaptan treatment was –1.95 kg, with the 50% of patients experiencing a 2 kg/week reduction. Spot urinary sodium was found to be a better predictor of tolvaptan response than liver function and liver fibrosis markers. Median survival was significantly longer (not reached versus 116 days, p = 0.005) and serum creatinine concentrations 12 weeks after tolvaptan administration significantly lower (0.99 vs. 1.55 mg/dL, p < 0.05) in the Decreased than in the Not-decreased group. Multivariate analysis showed that the presence of viable hepatocellular carcinoma (hazards ratio [HR] 2.14, p = 0.02) and a decrease in diuretics were independently prognostic of survival (HR 0.36, p < 0.01). Conclusions: The maintenance of renal function is essential in enhancing survival of patients with cirrhosis. Doses of diuretics should be adjusted appropriately during tolvaptan treatment.

Effects of Long- and Intermediate-Acting Dihydropyridine Calcium Channel Blockers in Hypertension: A Systematic Review and Meta-Analysis of 18 Prospective, Randomized, Actively Controlled Trials.

Dihydropyridine calcium channel blockers are a heterogeneous group of antihypertensive drugs. Long-acting dihydropyridine agent amlodipine is widely used for monotherapy and combination therapy for hypertension in clinical practice, while intermediate-acting dihydropyridine agents have shown inconsistent results in randomized clinical trials (RCTs). A meta-analysis of 18 RCTs enrolling a total of 80,483 patients with hypertension followed for a mean of 51.4 months was performed. Amlodipine therapy was associated with 25% higher risk of heart failure (relative risk [RR]: 1.25, 95% confidence interval [CI], 1.05-1.49, P = .019) but 17% lower risk of stroke (RR: 0.83, [95% CI, 0.72-0.97], P = .009) without statistically significant effect on acute myocardial infarction (AMI) compared to major alternative antihypertensive therapy (MAAT), including β-blocker, diuretic, angiotensin-converting enzyme inhibitor, or angiotensin-receptor blocker. Intermediate-acting dihydropyridine calcium channel blocker therapy was associated with 25% higher risk of heart failure (RR: 1.25, [95% CI, 1.06-1.47], 0.005, P = .005) and 26% higher risk of AMI (RR: 1.26, [95% CI, 1.05-1.51], 0.019, P = .019) compared to MAAT. Results of the subgroup analysis suggested that the intermediate-acting dihydropyridine calcium channel blocker was associated with higher risk of heart failure (RR: 1.30, [95% CI, 1.08-1.56], P = .005) and AMI (RR: 1.50, [95% CI, 1.01-2.22], P = .043) compared to renin-angiotensin system blockers and a trend toward higher risk of AMI (RR: 1.17, [95% CI, 0.99-1.38], P = .064) compared to conventional therapy, including β-blockers and diuretics. Meta-regression analyses suggested that long-acting dihydropyridine calcium channel blocker is associated with lower risk of AMI ( B: -0.327, [95% CI, -0.530 to -0.123], P = .002) with a trend toward lower risk of stroke ( B: -0.203, [95% CI, -0.410 to 0.003] P = .054). This study suggests that Amlodipine offers greater protection against major complications of hypertension compared to intermediate-acting dihydropyridine calcium channel blockers.

Changes in red blood cell volume during transition of heart failure status: a reflection of cellular hydration status?

This study examined how changes in heart failure (HF) status induce changes in the index of erythrocyte hydration based on mean red blood cell volume (MCV). Data from 47 HF patients (32% men; 78.2 ± 9.7 years) that experienced worsening and recovery of HF were analysed. Blood tests included measurements of MCV, albumin, serum solutes and b-type natriuretic peptide (BNP). Among a total of 47 worsening HF events, changes in MCV were positively correlated with changes in body weight (r = 0.31, p = .034), serum sodium (r = 0.417, p = .0036), and chloride (r = 0.457, p = .0012), and negatively correlated with changes in blood urea nitrogen (r= −0.389, p = .0069) and creatinine (r= −0.494, p = .0004). At recovery from worsening of HF by conventional diuretic therapy, change in MCV was positively correlated with the change in body weight (r = 0.457, p = .0012), serum sodium (r = 0.466, p = .001) and chloride (r = 0.484, p = .0006). Multivariate regression analysis demonstrated an independent association between the increase in serum chloride and MCV from stability to worsening of HF (odds ratio [OR] 6.02, 95% confidence interval [CI] 1.09–33.2, p = .039) and the increase or absence of change in serum chloride concentration and preserved MCV after decongestion (OR 11.5, 95% CI 1.53–85.9, p = .017). In conclusion, this study demonstrates that the changes in MCV under transition in HF status do not reflect a change that occurs in parallel with changes in HF-related markers, such as body weight and serum BNP level, but is independently associated with a change in the serum chloride concentration. Whether changes in MCV actually reflect the bodily cellular hydration status warrants further research.

The effects of tolvaptan dose on cardiac mortality in patients with acute decompensated heart failure after hospital discharge.

Tolvaptan (TLV) is a newly developed oral vasopressin-2 receptor antagonist that is mostly used for patients with acute decompensated heart failure (ADHF) refractory to conventional diuretic therapy. The aim of this study was to investigate the effects of outpatient TLV dose on cardiac mortality in patients discharged after hospitalization for ADHF. One hundred and five patients with ADHF who had been treated with TLV for the first time during hospitalization were retrospectively divided into three groups based on outpatient TLV use and dose. The non-TLV group comprised patients who were not treated with TLV after discharge (n = 36). Patients who continued TLV after discharge were further classified into two groups: low-dose (LD)-TLV (3.75mg/day, n = 27) and high-dose (HD)-TLV (7.5 or 15mg/day, n = 42). The primary endpoint was cardiac mortality. Secondary endpoint included the composite of all-cause mortality or re-hospitalization due to worsening of ADHF. There were no significant differences in demographic variables other than body mass index (p = 0.0026), echocardiographic data, laboratory data other than serum chloride before TLV administration (p = 0.041), serum sodium (p = 0.040) and potassium (p = 0.027) at discharge, and concomitant medications among the three groups. The Kaplan-Meier curve showed that the survival rate was lower in HD-TLV than in non-TLV, whereas LD-TLV showed the highest survival rate among the three groups (p = 0.0001). Multivariable Cox regression analysis of the clinical characteristics used for predicting cardiac mortality revealed that LD-TLV (hazard ratio [HR] 0.16, 95% confidence interval [CI] 0.01-0.93, p = 0.040) and HD-TLV (HR 2.43, 95% CI 1.06-6.26, p = 0.035) were significant predictors after adjustment for predictive covariates. In conclusion, the judgement of the continuation of LD-TLV according to patient hemodynamics and severity of congestion may not cause worsened prognosis.

Can Tolvaptan Protect Renal Function in the Early Postoperative Period of Cardiac Surgery? - Results of a Single-Center Randomized Controlled Study.

Oral administration of tolvaptan, a vasopressin V2receptor antagonist, significantly reduces deterioration of renal function, which has recently been highlighted as an exacerbating factor for adverse events in patients with acute heart failure. In the present study we tested the hypothesis that concomitant administration of tolvaptan with a conventional diuretic is beneficial for perioperative body fluid management in patients who have undergone cardiac surgery.Methods and Results:In all, 280 patients who underwent cardiac surgery were prospectively randomized to concomitant treatment with tolvaptan and a conventional diuretic (tolvaptan group; 147 patients) or treatment with a conventional diuretic alone (control group; 133 patients). Groups were compared in terms of the time required to restore preoperative body weight and the incidence of worsening renal function (WRF), defined as an increase in the serum creatinine level ≥0.3 mg/dL. The time required to restore preoperative body weight was significantly shorter in the tolvaptan than control group (mean [±SD] 3.97±1.95 vs. 5.02±2.83 days, respectively; P<0.001). The incidence of WRF was significantly lower in the tolvaptan than control group (n=11 [7.5%] vs. n=25 [18.8%], respectively; P=0.011). Administration of tolvaptan with conventional diuretics in the early postoperative period after cardiac surgery could be beneficial in maintaining urine output without affecting renal function and may thus help avoid WRF.

Powerful diuretics: A common denominator in landmark hypertension and type 2 diabetes mellitus trials.

Powerful diuretics: A common denominator in landmark hypertension and type 2 diabetes mellitus trials.

Why do SGLT2 inhibitors reduce heart failure hospitalization? A differential volume regulation hypothesis.

The effect of a sodium glucose cotransporter 2 inhibitor (SGLT2i) in reducing heart failure hospitalization in the EMPA-REG OUTCOMES trial has raised the possibility of using these agents to treat established heart failure. We hypothesize that osmotic diuresis induced by SGLT2 inhibition, a distinctly different diuretic mechanism than that of other diuretic classes, results in greater electrolyte-free water clearance and, ultimately, in greater fluid clearance from the interstitial fluid (IF) space than from the circulation, potentially resulting in congestion relief with minimal impact on blood volume, arterial filling and organ perfusion. We utilize a mathematical model to illustrate that electrolyte-free water clearance results in a greater reduction in IF volume compared to blood volume, and that this difference may be mediated by peripheral sequestration of osmotically inactive sodium. By coupling the model with data on plasma and urinary sodium and water in healthy subjects who received either the SGLT2i dapagliflozin or loop diuretic bumetanide, we predict that dapagliflozin produces a 2-fold greater reduction in IF volume compared to blood volume, while the reduction in IF volume with bumetanide is only 78% of the reduction in blood volume. Heart failure is characterized by excess fluid accumulation, in both the vascular compartment and interstitial space, yet many heart failure patients have arterial underfilling because of low cardiac output, which may be aggravated by conventional diuretic treatment. Thus, we hypothesize that, by reducing IF volume to a greater extent than blood volume, SGLT2 inhibitors might provide better control of congestion without reducing arterial filling and perfusion.

Readmission rates after Acute Decompensated Heart Failure

Introduction: Acute Decompensated Heart Failure (ADHF) is a major health concern worldwide. Ultrafiltration (UF) versus Conventional Diuretics (CD) in ADHF treatment has been studied in several trials with variable outcomes. Objective: To determine if UF is superior to CD in reducing readmissions after ADHF. Methods: MEDLINE was searched using PUBMED for potential studies. Total studies found=590, Total trials=34, Randomized control trials (RCT) = 9 were included (n=820, UF=403, CD =417). RevMan Version 5.3 Copenhagen was used for statistical analysis. Sensitivity analysis was done for heterogeneity. Results: Baseline characteristics were similar in both groups. Mean age was 66 years and 74% were males. Mean EF was 32.9%. Total of 188 patients were readmitted secondary to ADHF with 77 in UF group vs 111 in CD group; RR was 0.71 (95% CI, 0.49-1.02, p=0.07, I2=47%) . There was significantly reduced number of readmissions at 90 days 43 vs 67 in favor of UF; RR was 0.65 (95% CI, 0.47-0.90, P=0.01, I2= 0%). Fluid removal and weight change were significantly higher in UF compared to CD. Change in creatinine pre and post intervention and the number of acute kidney injury were similar in both groups. There was also no difference in the length of hospital stay. Hypotension was more common in UF group compared to CD group (24 vs 13, OR = 2.06, 95%CI = 0.98-4.32, P=0.06, I2=0%) but it was statistically insignificant. Major Adverse Cardiovascular Events (MACE) and mortality was also similar in both groups. Sensitivity analysis was done for heterogeneity and is reported using I2. Conclusions: In this meta-analysis, UF was associated with significantly reduced heart failure readmissions at 90 days and there was trend towards reduced cumulative hospital readmissions. There was no difference in renal outcomes, fluid removal, weight loss, MACE and length of hospital stay in either intervention group.

Prognostic Impact of Mild Hypokalemia in Terms of Death and Stroke in the General Population—A Prospective Population Study

BackgroundPotassium supplementation reduces the risk of cardiovascular mortality and stroke in population studies; however, the prognostic impact of mild hypokalemia in the general population has not been thoroughly investigated. We aimed to investigate associations between mild hypokalemia and endpoints in the general population. MethodsParticipants (aged 48-76 years) from the general population study “Copenhagen City Heart Study” (n = 5916) were studied. Participants were divided into groups according to baseline values of plasma potassium (potassium): hypokalemia (<3.7 mmol/L, n = 758), normokalemia (3.7-4.5 mmol/L, n = 4973), and high potassium (>4.5 mmol/L, n = 185). Hypokalemia was further divided as potassium <3.4 mmol/L and 3.4-3.6 mmol/L. The primary endpoints were all-cause mortality and nonfatal validated ischemic stroke. The secondary endpoint was acute myocardial infarction (AMI). We adjusted for conventional risk factors, diuretics, and atrial fibrillation at baseline. ResultsMean potassium in the hypokalemic group was 3.5 mmol/L (range, 2.6-3.6 mmol/L) and was associated (P < 0.05) with increased systolic blood pressure, higher CHA2DS2-VASc score, and increased use of diuretics as compared with normokalemia. Baseline atrial fibrillation was equally frequent across groups. Median follow-up-time was 11.9 years (Q1-Q3: 11.4-12.5 years). Hypokalemia was borderline associated with increased stroke risk in a multivariable Cox model (including adjustment for competing risk) as compared with normokalemia (hazard ratio [HR] 1.40; 95% confidence interval [CI], 1.00-1.98). The subgroup with potassium <3.4 mmol/L had higher stroke risk (HR 2.10; 95% CI, 1.19-3.73) and mortality risk (HR 1.32; 95% CI, 1.01-1.74) as compared with normokalemia. Hypokalemia was not associated with AMI, and no increased risk of mortality was seen with concomitant AMI and hypokalemia. No associations were seen with high potassium. ConclusionIn a general population mild hypokalemia is associated with increased stroke risk and, to a lesser degree, increased mortality risk.

Safety and effectiveness of tolvaptan for fluid management after pediatric cardiovascular surgery.

Postoperative fluid management is important after open heart surgery, because cardiopulmonary bypass evokes an abnormal inflammatory response and increases vascular permeability, especially in pediatric patients. We assessed the safety and effectiveness of tolvaptan for management of postoperative fluid retention after congenital heart surgery. This retrospective study analyzed data from 43 children with uncomplicated congenital heart disease who underwent open heart surgery between September 2013 and August 2016. The patients were divided into two groups. Group N (n=18; September 2013 through May 2014) received the conventional oral diuretics alone, and Group T (n=25; June 2014 through August 2016) received a single dose of tolvaptan (0.45mg/kg) in addition to the conventional oral diuretic therapy. Data were collected, while patients who received intensive care were assessed and compared between groups. Add-on tolvaptan use was associated with increased urinary output standardized by body weight (54.3±4.5 vs 47.3±19.1mL/kg; p=0.043), decreased additional intravenous diuretic dose standardized by body weight (0.26±0.23 vs 0.62±0.48mg/kg; p=0.001), and a smaller decrease in central venous pressure (1.3±2.7 vs 1.9±3.8mmHg; p=0.019). Laboratory analysis showed that electrolyte concentrations in blood and urine did not significantly differ between groups. Tolvaptan appears to be effective and safe for management of postoperative fluid retention after congenital heart surgery.

The use of nesiritide in patients with critical cardiac disease.

We evaluated the use of nesiritide in children with critical CHD, pulmonary congestion, and inadequate urine output despite undergoing conventional diuretic therapy. We conducted a retrospective analysis of 11 patients with critical CHD, comprising 18 infusions, each of which occurred during separate hospitalisations. Haemodynamic parameters were assessed, and the stage of acute kidney injury was determined before and throughout the duration of therapy using a standardised definition of acute kidney injury - The Kidney Disease: Improving Global Outcomes criteria. Patients Children with critical CHD, pulmonary congestion, and inadequate urinary output despite undergoing diuretic therapy were included. Measurements and main results The use of nesiritide was associated with a significant decrease in the maximum and minimum heart rate values and with a trend towards a significant decrease in maximum systolic blood pressure and maximum and minimum central venous pressures. Urine output increased but was not significant. Serum creatinine levels decreased significantly during the course of therapy (-0.26 mg/dl [-0.50, 0.0], p=0.02), and the number of patients who experienced a decrease in the stage of acute kidney injury of 2 or more - where a change in the stage of acute kidney disease of 2 or more was possible, that is, baseline stage >1 - was highly significant (five of 12 patients, 42%, p<0.001). Nesiritide had a favourable impact on haemodynamics, and its use was not associated with deterioration of renal function in patients with critical CHD.

Hyponatraemia and congestive heart failure refractory to diuretic treatment. Utility of tolvaptan

Heart failure (HF) is currently one of the most significant healthcare problems in Spain and has a continuously increasing prevalence. Advances in our understanding of the various biological responses that promote cardiac remodeling and pulmonary venous congestion constitute the basis of current treatment.This article, prepared by members of the HF groups of the Spanish Society of Cardiology and the Spanish Society of Internal Medicine, discusses the current therapeutic strategies for patients with congestion refractory to diuretic treatment. The article includes our clinical experience with the use of tolvaptan as an additional treatment for congestion associated with hyponatraemia. To this end, we propose an algorithm for the use of tolvaptan in patients with congestive HF, natraemia <130mEq/L and poor response to conventional diuretic treatment.

Hiponatremia e insuficiencia cardiaca congestiva refractaria a tratamiento diurético. Utilidad del tolvaptán

Heart failure (HF) is currently one of the most significant healthcare problems in Spain and has a continuously increasing prevalence. Advances in our understanding of the various biological responses that promote cardiac remodelling and pulmonary venous congestion constitute the basis of current treatment.This article, prepared by members of the HF groups of the Spanish Society of Cardiology and the Spanish Society of Internal Medicine, discusses the current therapeutic strategies for patients with congestion refractory to diuretic treatment. The article includes our clinical experience with the use of tolvaptan as an additional treatment for congestion associated with hyponatraemia. To this end, we propose an algorithm for the use of tolvaptan in patients with congestive HF, natraemia <130mEq/l and poor response to conventional diuretic treatment.

Prediction of diuretic response to tolvaptan by a simple, readily available spot urine Na/K ratio.

BackgroundTolvaptan is vasopressin type 2 receptor antagonist that inhibits water reabsorption. It is used in combination with standard diuretics to treat ascites unresponsive to standard diuretic therapy or hyponatremia because of liver cirrhosis. This study evaluated the effectiveness and safety of tolvaptan in clinical practice and aimed to determine the factors related to its effectiveness.MethodsTolvaptan was administered to 88 consecutive cirrhotic patients with ascites unresponsive to standard diuretic therapy. An effective treatment response was a ≥2% reduction in body weight on day 7. The association of patient pretreatment characteristics with therapeutic effects was analyzed.ResultsMean weight reduction on day 7 of tolvaptan therapy was −2.9% ± 3.2%, and treatment was effective in 52% of patients. Multivariate analysis revealed that spot urine Na/K ratio ≥2.5 at baseline was the only factor independently related to therapeutic effect, with an odds ratio of 7.85 (95% confidence interval 2.64–23.40, p = 0.0002). Weight reduction percentage on day 7 was −4.0% ± 2.8% in patients with spot urine Na/K ≥2.5, which was significantly greater than the 0.7% ± 2.7% loss in those with urine Na/K < 2.5 (p < 0.05). A spot urine Na/K ratio ≥2.5 had a sensitivity of 85% and specificity of 60% for predicting effective treatment. No adverse events of treatment led to treatment discontinuation.ConclusionsBaseline spot urine Na/K was predictive of an effective response to tolvaptan therapy. It is simple to perform and readily available and might serve as an indicator of optimal timing of tolvaptan administration in patients with inadequate response to conventional Na diuretic therapy.

New findings of dopamine in renal protection and treatment of septic shock

Background Recently, it was reported that dopamine in renal protection and treatment of septic shock showing a variety of uncertain results, caused a lot of controversy. Objective Review the effects of dopamine in renal protection and treatment of septic shock. Content According to the basic and clinical aspects on dopamine, we investigated the efficacy and safety of dopamine. Although there are a large number of reports on the renal protective effect of dopamine, the conclusions are not consistent. Generally, application of dopamine in protecting renal function has no obvious benefit and is not superior to conventional diuretics. In the treatment of septic shock, dopamine should be carefully chosen because of the obviously potential side effects. Trend In critically ill patients, studies should be focused on the combination of diuretics and small dose of dopamine. More and more evidences on septic treatment support norepinephrine as the first-choice drug but not dopamine. Key words: Dopamine; Kidney; Septic Shock

Effectiveness and safety of tolvaptan in liver cirrhosis patients with edema: Interim results of post-marketing surveillance of tolvaptan in liver cirrhosis (START study).

Loop diuretics and spironolactone are used in patients with hepatic edema, but they are sometimes associated with insufficient responses as well as adverse events. Tolvaptan, a vasopressin type 2 receptor antagonist, was approved for hepatic edema in 2013. A large-scale post-marketing surveillance study has been carried out to evaluate the effectiveness and safety of tolvaptan in real-world clinical settings. Patients with hepatic cirrhosis with insufficient response to conventional diuretics were enrolled. The observational period was up to 6months. Changes in body weight and clinical symptoms were measured to evaluate effectiveness. The incidence of adverse drug reactions was summarized as a safety measure. Of 970 patients enrolled, 463 were included in the safety analysis. Of this group, 340 were included in the effectiveness analysis. Decreases in body weight from baseline were -2.38kg on day 7 and -3.52kg on day 14. Ascites and bloated feeling was significantly improved within 14days. The mean change in body weight depended on estimated glomerular filtration rate levels. The most frequently reported adverse drug reaction was thirst (6.9% of patients). Serum sodium level of ≥146mEq/L was observed in 12 patients (2.7%). In the real-world clinical setting, tolvaptan showed aquaretic effectiveness in patients with cirrhosis. The mean change in body weight depended on renal function. We recommend tolvaptan use for hepatic cirrhosis at a stage in which the renal function is maintained.

The Use of Nesiritide in Children With Congenital Heart Disease.

We evaluated the use of nesiritide in children with critical congenital heart disease, pulmonary congestion, and inadequate urine output despite conventional diuretic therapy. We conducted a retrospective analysis of 26 consecutive patients, comprising 37 infusions occurring during separate hospitalizations. Hemodynamic variables, urine output, and serum creatinine levels were monitored prior to and throughout the duration of therapy with nesiritide. In addition, the stage of acute kidney injury was determined prior to and throughout the duration of the therapy using a standardized definition of acute kidney injury-The Kidney Disease: Improving Global Outcomes criteria. Cardiac ICU. Pediatric patients with critical congenital heart disease, pulmonary congestion, and inadequate urinary output despite diuretic therapy. Nesiritide infusion. The use of nesiritide was associated with a significant decrease in the central venous pressure and heart rate with a trend toward a significant increase in urine output. During the course of therapy with nesiritide, the serum creatinine and stage of acute kidney injury decreased significantly. The decrease in stage of acute kidney injury became significant by day 4 (p = 0.006) and became more significant with time (last day of therapy compared with baseline; p < 0.001). During 12 of the 37 infusions, the stage of acute kidney injury decreased by two or more (p < 0.001). Nesiritide had a favorable impact on hemodynamics and urine output in children with critical congenital heart disease and pulmonary congestion, and there was no worsening of renal function.