Unsolved challenges in diuretic therapy for acute heart failure: a focus on diuretic response

Loop diuretics represent the mainstay of management of patients hospitalized for heart failure (HF). Diuretic resistance is commonly encountered in clinical practice, but limited evidence-based approaches are available to address it. Recent clinical investigations have proposed common definitions of diuretic response: a change in body weight, net fluid loss or total urinary output to 40 mg of furosemide dose equivalents. Poor diuretic response is characterized by features of advanced HF and atherosclerosis and is independently associated with poor in-hospital and post-discharge outcomes. A number of adjunctive or combination decongestion therapies are available to overcome diuretic resistance, but high-quality prospective data supporting these approaches are lacking. Once a definition has been standardized and accepted, diuretic response may represent an important inclusion criteria and end point in upcoming clinical trials in hospitalized HF to help define an optimal, tailored approach to this challenging clinical entity.     

强化利尿在慢性心力衰竭急性失代偿期治疗中的价值

目的 评价强化利尿治疗慢性心力衰竭(CHF)急性失代偿期的有效性、安全性及其对患者住院天数和费用的影响.方法 回顾性分析2006年1月1日至2007年9月1日福建医科大学附属协和医院心内科诊断为CHF心功能Ⅲ～Ⅳ级患者的临床资料.以入院后第2日的24 h尿量为标准分为≥2 400 ml组(强化利尿组)和<2 400 ml组(非强化利尿组)两组,观察强化利尿前后生化指标和生命体征的变化,比较两组住院期间的病死率和住院天数、费用的差异.结果 共195例患者入选,其中强化利尿组73例,非强化利尿组122例.强化利尿组住院期间的病死率低于非强化利尿组(1.4%比9.8%,P<0.05),住院天数、总费用和平均费用的中位数均低于非强化利尿组[住院天数:11 d比16 d;总费用:8 483元比12 182元;平均费用I:721.1元/日比854.4元/日;平均费用Ⅱ(不包括检查费):580.0元/日比698.2元/日,P<0.05或P<0.013.强化利尿治疗前后生化指标和心率变化差异无统计学意义;但强化利尿后的收缩压和舒张压均低于入院时水平[收缩压:(118.2±16.9)mm Hg比(127.0±24.9)mm Hg;舒张压:(67.2±4.5)mm Hg比(75.2±4.9)mm Hg,1 mm Hg=0.133 kPa.P<0.05和P<0.013.所有患者均未出现头晕、胸闷等低血压症状.结论 强化利尿治疗对CHF急性失代偿期患者安全有效,可减少患者住院天数和费用以及住院病死率.

Abstract：

Objective To evaluate both the efficacy,safety,length of stay in hospital and expenses of aggressive diuretic therapy in patients with acute decompensation of chronic heart failure(CHF).Methods The retrospective analysis was conducted in the patients with acute decompensation CHF New York Heart Association (NYHA) class Ⅲ or Ⅳ in department of cardiology of Fujian Medieal University Union Hospital from January 1st 2006 to September 1st 2007.The 24-hour urine volume on the 2nd day was equivalent or over 2 400 ml was defined as aggressive diuretic therapy group,and those with less than 2 400 ml of urine as non-aggressive diuretic therapy group.The biochemical parameters and vital signs were compared before and after aggressive diuretic therapy,and the mortality,the length of stay and expenses were also compared between the two groups.Results One hundred and ninety-five patients were enrolled in the study,there were 73 and 1 22 patients in aggressive diuretic therapy group and in non-aggressive diuretic therapy group respectively.The mortality in aggressive diuretic therapy group was lower than that in non-aggressive diuretic therapy group(1.4%vs.9.8%,P<0.05).The length of stay,total expenses and average cost in aggressive diuretic therapy group were lower than those in non-aggressive diuretic therapy group r espectively [the length of stay:11 days vs.16 days;total expenses:8 483 yuan vs.12 182 yuan;average expense I:721.1 yuan/d vs.854.4 yuan/d;average expense Ⅱ (except for examination expenses):580.0 yuan/d vs.698.2 yuan/d,P<0.05 or P<0.01].There were no significant changes in biochemical parameters and heart rate before and after aggressive diuretic therapy.The systolic pressure (SBP) a nd diastolic pressure (DBP) were reduced significantly after aggressive diuretic therapy[SBP:(118.2±16.9)mm Hg vs.(127.0±24.9)mm Hg;DBP:(67.2±4.5)mm Hg vs.(75.2±4.9)mm Hg,1 mm Hg=0.133 kPa,P<0.05 and P<0.01].No hypotension symptoms such as dizziness and chest distress were found in all patients. Conclusion Aggressive diuretic therapy in patients with acute decompensation CHF is a safe,effective mode of therapy.It can reduce the length of stay in hospital,experses and the mortality during hospitalization.     

Fluid management and diuretic therapy in acute renal failure

Acute renal failure (ARF) is a common problem in critical care; therefore, nurses should consider it to be a potential issue for all of their patients. Fluid management and diuretic therapy are important in these patients. The aim of this study is to review the use of these interventions in patients in acute renal failure. Initially, the paper will review renal physiology and discuss some of the causes of acute renal failure. This will be followed by a critical examination of the evidence surrounding the use of crystalloids and colloids for fluid resuscitation, as well as the role of diuretics in patients with acute renal failure. The paper concludes by identifying approaches for developing future practice in this area.     

Sodium and water retention in heart failure and diuretic therapy: basic mechanisms

The pathophysiology of sodium and water retention in heart failure is characterized by a complex interplay of hemodynamic and neurohumoral factors. Relative arterial underfilling is an important signal that triggers heart failure-related sodium and water retention. The response to perceived arterial underfilling is modulated by the level of neurohormonal activation, the degree of renal vasoconstriction, and the extent to which renal perfusion pressure is reduced. Sodium retention can also be exceeded by water retention, with the result being dilutional hyponatremia. Sodium and water retention in heart failure also function to dampen the natriuretic response to diuretic therapy. The attenuated response to diuretics in heart failure is both disease-specific and separately influenced by the rate and extent of diuretic absorption, the rapidity of diuretic tubular delivery, and diuretic-related hypertrophic structural changes that surface in the distal tubule.     

Markers of diuretic resistance in emergency department patients with acute heart failure

Background

Loop diuretics are common therapy for emergency department (ED) patients with acute heart failure (AHF). Diuretic resistance (DR) is a term used to describe blunted natriuretic response to loop diuretics. It would be important to detect DR prior to it becoming clinically apparent, so early interventions can be initiated. However, several definitions have been proposed, and it is not clear if they identify similar patients. We compared these definitions and described the clinical characteristics of patients who fulfilled them.

Methods

To qualify for this secondary analysis of 1033 ED patients with AHF, all patients needed to receive intravenous diuretics in the ED and have urine available within 24 h of their ED evaluation. A poor diuretic response, suggesting DR, was characterized by (1) a fractional sodium excretion (FeNa) of less than 0.2%; (2) spot urinary sodium of less than 50 meq/L; and (3) a urinary Na/K ratio <1.0. McNemar’s test was used to compare the different cohorts identified by the three definitions. Secondary analyses evaluated associations between each DR definition and hospital length of stay (LOS), ED revisits and rehospitalizations for AHF, and mortality using the Wilcoxon rank-sum tests and linear regression or Pearson chi-square test and logistic regression, as appropriate.

Results

The median age of the 187 patients was 64, and 50% were African-American. There were 5.9% of patients with a FeNa less than 0.2%, 17.1% had urinary sodium less than 50 meq/L, and 10.7% had a urinary Na/K ratio <1.0. The three definitions identified significantly different patients with very little overlap (p?<?0.02 for all comparisons). There were 37 (19.8%) patients who were readmitted to the ED or hospital or died within 30 days of ED evaluation. Patients with spot urinary sodium less than 50 meq/L were more likely to be readmitted (p?=?0.03).

Conclusions

The patient proportion with poor natriuresis and DR varies depending on the definition used. Early ED therapy would be impacted at different rates if clinical decisions are made based on these definitions. These findings need to be further explored in a prospective ED-based study.

Trial registration

ClinicalTrials.gov, NCT00508638

     

Nesiritide therapy for acute heart failure

Each year, more than 1 million hospitalizations are the result of heart failure. Acute exacerbations of heart failure can occur following routine surgical procedures. One of the newest pharmacological therapies for heart failure is nesiritide. The PACU nurse's vital role in the early recognition and early intervention of heart failure may include the administration of this agent.     

The benefits of early vasoactive therapy in the treatment of acute decompensated heart failure

PURPOSE: To review current issues in the management of acute decompensated heart failure (ADHF), focusing on the early initiation of intravenous (i.v.) vasoactive therapy and including the effects of vasoactive drugs on patient outcomes and the benefits and limitations of each medication class. DATA SOURCES: Review of the worldwide scientific literature on ADHF. CONCLUSIONS: The management of ADHF may be improved by early initiation of i.v. vasoactive therapy, reduced use of inotropic agents, and judicious use of diuretics. Data to date suggest that early treatment with the natriuretic peptide nesiritide reduces duration of hospitalization, in-hospital mortality, and requirements for i.v. inotropes and diuretics. IMPLICATIONS FOR PRACTICE: Advance practice nurses play an integral role in the management of patients with ADHF from initial triage in the emergency department through final discharge from the hospital. Because they are typically responsible for administering medications and monitoring patient status, nurses need to be familiar with the benefits and limitations of each class of vasoactive agent. They need to recognize that prompt initiation of i.v. vasodilator therapy is important for improving patient outcomes. Further, advance practice nurses should participate in team management that promotes the use of evidence-based ADHF care by developing, using, and assertively communicating the need for processes of care that facilitate best practices.     

Rational diuretic management in congestive heart failure: a case-based review

The pharmacology and pharmacokinetics of diuretics are unique among therapeutic drugs. Knowledge of these principles can be used to great advantage in the management of heart failure, whereas ignoring them can lead to either minor or life-threatening adverse consequences. Two major categories of potential therapeutic problems are diuretic resistance and the development of disturbances in serum potassium and other electrolytes. Inhibition of sodium reabsorption in the loop of Henle or distal convoluted tubule leads to renal potassium wasting, whereas inhibition of sodium reabsorption in the collecting duct (either directly, as with triamterene or amiloride, or through aldosterone antagonism) causes potassium retention. Combining diuretics of different classes, a rational and frequently used strategy to counter diuretic resistance, can be anticipated to balance or magnify these effects, depending on the site of action of the individual drugs.     

Loop diuretic strategies in patients with acute decompensated heart failure: A meta-analysis of randomized controlled trials

Purpose

The safety and efficacy of continuous infusion vs bolus injection of intravenous loop diuretics to treat acute decompensated heart failure were debated. Our aim is to compare the administration routes of diuretics in hospitalized patients with acute decompensated heart failure.

Methods

A systematic review and meta-analysis of randomized controlled trials was performed to evaluate the effects of continuous infusion vs bolus administration of loop diuretics in patients with acute decompensated heart failure. The primary end points were urine outputs, body weight loss, all causes of mortality, and death from cardiovascular causes. Secondary end points were electrolyte imbalance, change in creatinine levels, tinnitus or hearing loss, and days of hospitalization.

Results

Ten randomized controlled trials with 518 patients were identified. Continuous infusion of diuretics was associated with a significantly greater weight loss (weighted mean difference, 0.78; 95% confidence interval, 0.03-1.54) compared with bolus injection. Urine output, the incidence of electrolyte imbalance, change in creatinine level, length of hospitalization, the incidence of ototoxicity, cardiac mortality, and all-cause mortality showed no significant differences between the 2 groups.

Conclusion

Meta-analysis of the existing limited studies did not confirm any significant differences in the safety and efficacy with continuous administration of loop diuretic, compared with bolus injection in patients with acute decompensated heart failure.     

利尿剂降阶梯治疗中节点选择对急性左心衰竭患者的影响

目的探讨利尿剂降阶梯治疗中节点选择对急性左心衰竭患者的影响。方法将我院收治的60例急性左心衰竭患者采用数字法随机分组模式分为A组与B组,各30例。所有患者均给予常规综合治疗与利尿剂降阶梯治疗,A组以血清D-D水平高于正常值(>75μg/L)为节点;B组以氨基末端脑钠肽前体(NT-proBNP)较治疗前降低30%为节点。比较两组的治疗效果。结果B组的PaO2、PaCO2水平及PaO2/FiO2均明显优于A组(P<0.05)。B组肺水肿缓解率高于A组(P<0.05)。B组的不良反应总发生率低于A组(P<0.05)。结论采用利尿剂降阶梯治疗急性左心衰竭患者时以NT-proBNP降低30%为节点有助于改善其通气状态,提高治疗安全性,值得临床推广。     

早期机械通气治疗急性左心衰竭的临床研究

目的:探讨机械通气在急性左心衰竭治疗中的应用时机选择。方法:将32例采用早期机械通气的急性左心衰患者作为治疗组,28例未采用早期机械通气的患者作为对照组,观察两组患者机械通气后0.5h、1h、3h的呼吸频率(RR)、动脉血氧分压(PaO2)、心率(HR)、平均动脉压(MAP)等变化情况,及患者住院病死率。结果:两组患者机械通气后0.5、1、3h的RR、PaO2、HR、MAP较通气前有明显改善(P<0.05);治疗组中30例缓解,2例死亡,对照组中20例缓解,8例死亡,两组住院病死率差异有统计学意义(P<0.05)。结论:在救治急性左心衰患者时尽早应用机械通气能有效改善低氧血症、提高抢救成功率。     

Extracorporeal ultrafiltration therapy for acute decompensated heart failure

Congestion is the most common reason for hospitalization of patients with acute decompensated heart failure (ADHF) and adversely impacts their outcomes. Extracorporeal ultrafiltration (UF) therapy has re-emerged as an effective strategy for decongestion in this setting. This article is intended to discuss key concepts in UF and its technique, provide a brief historical view of UF application for decongestion in ADHF, review the hemodynamic and neurohormonal effects of UF and their positive effects on the pathophysiology of ADHF, discuss the findings of the landmark trials in this field, and explain key findings of these studies as well as the apparent discrepancies in their findings. In a separate section we discuss the intricacies of renal dysfunction in ADHF as it plays a very important role in understanding the current evidence and designing futures clinical trials of UF in ADHF. In the end, the authors provide their perspective on the future role of UF in management of patients with ADHF and congestion.     

A comparison of three diuretic regimens in heart failure

Abstract. Eight patients with mild heart failure were treated in random order for 1 week with 2 mg bumethanide at 0800 and 1200 (treatment I) h, 1 mg bumethanide at 0800, 1200, 1800, 2200 (treatment 2) and 5 mg bendroflumethiazide at 0800 and 1800 (treatment 3) h. The 'quality of life' did not differ significantly between the three treatment periods. At the presumed trough of the diuretic effect the circulating blood volume was largest during treatment 1; it was 6.3% smaller during treatment 2 ( P< 0.02) and 6.7%) lower during treatment 3 (P<0.05). In comparison with treatment 1, the maximal increase in rate-pressure product during physical exercise was 24.6% higher in treatment 3. Compared with treatment 1 the area under the curve (AUC) for plasma lactate during physical exercise was 14% lower during treatment 2 (P<0.05) and 18% lower during treatment 3 (P<0.01). These findings suggest that the type of program for diuretic therapy influences the magnitude of inevitable diurnal fluctuations in body fluids, the ability of the heart to work and the ability of the body to adjust to the oxygen demand.     

急性心力衰竭临床诊断和治疗的若干进展

急性心力衰竭(AHF)是常见急危重症,病死率和致残率极高.近年来AHF的临床研究进展主要集中在生物学标记物与AHF诊断、病情严重程度、预后评估以及新药物治疗等方面,本文简要述及生物学标记物和新药物治疗.