Clinical inquiries. Does furosemide decrease morbidity or mortality for patients with diastolic or systolic dysfunction?

No large-scale randomized, placebo-controlled trials evaluate furosemide's effect on mortality and long-term morbidity in diastolic or systolic dysfunction. In short-term studies, furosemide reduces edema, reduces hospitalizations, and improves exercise capacity in the setting of systolic dysfunction (strength of recommendation [SOR]: B, based upon low-quality randomized controlled trials). Furosemide and other diuretics reduce symptomatic volume overload in diastolic and systolic dysfunction (SOR: C, based on expert opinion). There is potential morbidity with the use of high-dose loop diuretics (volume contraction, electrolyte disturbances, and neuroendocrine activation). Use of high-dose loop diuretics for systolic dysfunction is associated with increased mortality, sudden death, and pump failure death (SOR: B, based on retrospective analyses of large-scale randomized controlled trials). However, diuretic resistance or disease severity may explain these latter findings.     

Are diuretics helpful in acute renal failure?

Although widely used to treat acute renal failure, diuretics may actually be harmful. The results of this observational study demonstrated a higher risk of death and non-recovery of renal function when diuretics were initiated during the first week of hospitalization. It didn't matter whether a single or combination diuretic was used. A randomized controlled trial would better answer this question by minimizing the inherent flaws in an observational study. Although this study doesn't conclusively prove that diuretics cause poorer outcomes, it certainly raises the possibility and should prompt us to think twice before initiating diuretic therapy for acute renal failure.     

Serum potassium testing in diuretic-treated outpatients. A multivariate approach

We evaluated risk factors for abnormal serum potassium (K+) concentrations in 5817 outpatients on chronic diuretic therapy. Hypokalemia (K+ less than 3.5 meq/L) occurred in 18.8 percent at the last clinic measurement. Hyperkalemia (K+ greater than 5.5) was rare (0.5%) and was even less common in those also taking KCl or a K+ sparing drug (0.2%). Hypokalemic patients were younger, healthier, more often hypertensive, more commonly taking a thiazide diuretic, and more likely to have been hypokalemic in the past. Hyperkalemic patients were older, more often suffering from heart or renal failure, and more commonly taking furosemide. Logistic regression analysis yielded eight variables that contributed significantly to the prediction of hypokalemia: mean and most recent serum K+, thiazide use, the use and duration of use of potassium-sparing diuretics, age, and most recent serum sodium and bicarbonate determinations. The regression equation allowed us to identify a group of patients (63% of the total) at low risk for hypokalemia (K+ less than 3.5 in 9.4%; K+ less than 3.0 in 0.5%) and another group (37% of the total) at high risk for hypokalemia (K+ less than 3.5 in 35%; K+ less than 3.0 in 5%). Information about the risk of hypokalemia can be used to decide when to measure serum potassium concentration in individual diuretic-treated outpatients.     

Anti-aldosterone therapy in severe heart failure]

The mortality rate among patients with severe heart failure is still very high despite treatment with loop diuretics and angiotensin-converting enzyme (ACE) inhibitors. The 'randomized aldactone evaluation study' (RALES) has shown that 25 mg spironolactone added to this treatment was safe and reduced all-cause mortality by 30% in patients with severe (previous New York Heart Association (NYHA) functional class IV) heart failure due to systolic left ventricular dysfunction. Blockade of aldosterone in these patients may be necessary to overcome so-called aldosterone escape during chronic ACE-inhibition. The beneficial effects of spironolactone may relate to enhanced diuresis, anti-arrhythmogenic properties and direct effects on the myocardium and blood vessels. At present, addition of spironolactone may be appropriate for patients with severe heart failure, whereas patients with moderate heart failure may benefit more from beta-blockade.     

Treating hypertension is more important than the choice of agent; results from the largest clinical trial until now

During the past few years, several randomised trials have compared the effects of older blood-pressure lowering drugs (diuretics, beta-blockers) with those of newer ones (angiotensin converting enzyme (ACE) inhibitors, calcium entry blockers) on the long-term prognosis. In general, no significant differences were found between these regimes. Recently, the ALLHAT trial, which was the largest hypertension trial ever and in which over 40,000 patients with hypertension participated, was completed. The initial treatment consisted of either the diuretic chlorthalidone, the calcium entry blocker amlodipine, the ACE inhibitor lisinopril, or the alpha-blocker doxazosin. The latter arm was prematurely discontinued because of a higher incidence of the secondary endpoint heart failure and stroke. Based on an intention-to-treat analysis, the other types of treatment proved to be equivalent in terms of the primary endpoint, a composite of fatal coronary heart disease and non-fatal myocardial infarction. Although the investigators conclude that ALLHAT suggests that thiazide diuretics should be first choice in the treatment of hypertension, there are several caveats that tend to lessen the strength of this conclusion.     

Dehydration in black and white older adults using diuretics

PURPOSE: To assess the association between dehydration and ethnicity in older adults; and to determine if diuretic use can help explain the disparity between blacks and whites in diagnosis of dehydration. METHODS: We conducted a case-control study in black and white older adults in a pharmaceutical assistance program who were hospitalized during 1997. Cases were all those diagnosed with dehydration (N=9186). Randomly selected controls were 4:1 frequency matched to cases by sex and age group (N(Total)=45585). RESULTS: Patients taking loop, potassium-sparing, thiazide or combination diuretics were more likely to have a diagnosis of dehydration. Dehydration diagnosis was associated with being black (odds ratio (OR)=1.49, 95% confidence interval (CI), 1.36-1.63, p<.001), independent of diuretic use or dosage. That association remained when examining loop (OR=1.36, 95% CI, 1.10-1.63, p<.004) and thiazide diuretic users (OR=1.59, 95% CI, 1.09-2.34, p=.017), but not potassium-sparing or combination diuretic users. CONCLUSION: Diuretic use is significantly associated with dehydration diagnosis, but the greater likelihood of older blacks being diagnosed with dehydration is independent of diuretic use. The increased risk of morbidity and mortality associated with dehydration suggests that further examination of the root cause of this disparity in risk is warranted.     

Diuretics and vitamin B1: are diuretics a risk factor for thiamin malnutrition?

Despite modern pharmacologic agents in the therapy of heart failure, the prevalence of heart failure is increasing worldwide. In the vitamin B1 deficiency disease beriberi, cardiac symptoms may represent the central feature. Two new studies confirmed that all diuretics lead to increased urinary thiamin excretion depending on the urinary flow rate. In a subject at risk, such as an elderly patient, chronic diuretic treatment may lead to a subclinical thiamin deficiency. Whether subclinical thiamin nutriture is a modulator of the prevalence and/or severity of heart failure is not known; however, it seems to be plausible from the metabolic point of view.     

Gout not induced by diuretics in a case-control study in general practice

OBJECTIVE: To determine the relation between diuretics and the development of gout, taking into account the possible confounding by hypertension and cardiovascular diseases. DESIGN: Case-control study. METHOD: With the aid of the data on morbidity and medication from the electronic medical files ofa dispensing general practitioner, all patients with a first gout registration during the period from October 1994 to September 2002 were identified as cases; in the same practice, for each patient, 3 controls of the same age and sex who were known not to have gout were selected at random. Conditional logistic regression analyses were carried out to estimate the odds ratio (OR) for gout in patients who had used diuretics for at least 3 months and in patients suffering from hypertension, heart failure, or myocardial infarction. The statistical interaction between variables was investigated after stratification for diuretic use. RESULTS: Via the medical files, 70 gout patients (59 men), with a mean age of 55.1 years (SD: 13.5) were identified, plus 210 matched controls. When assessed without correction, the use ofdiuretics seemed to be associated with a definite risk of gout: OR: 2.8 (95% CI: 1.2-6.6). But after adjustment for the cardiovascular variables hypertension, heart failure and myocardial infarction, the risk of gout associated with diuretic use disappeared: OR: 0.6 (95% CI: 0.2-2.0). An independent risk of gout was demonstrated for hypertension (OR: 3.9; 95% CI: 1.6-10.0), and to a lesser degree for myocardial infarction (OR: 1.5; 95% CI: 0-5-4.1). The risk of gout associated with heart failure was also calculated (OR: 40.1; 95% CI: 3.8-437.2), but diuretic independency could not be proven as all patients with heart failure were on diuretics and there was no heart failure among those not using diuretics. CONCLUSION: In this case-control study, the use of diuretics did not increase the risk of gout. The cardiovascular indications for prescribing diuretics were significant confounders.     

Guideline 'Chronic heart failure'

A new Dutch clinical practice guideline has been developed for the diagnosis, treatment and supportive care of patients with chronic heart failure. This has been formulated by a multidisciplinary working group, set up by the Netherlands Heart Foundation and the Netherlands Society of Cardiology, in cooperation with the Dutch Institute for Healthcare Improvement. Heart failure is defined as: 'a complex of complaints and symptoms resulting from an inadequate pumping function of the heart'. Indications for heart failure are dyspnoea on exertion, reduced exertion tolerance and oedema. By using data from the medical history, case history, physical examination and simple additional tests (laboratory tests, ECG, chest X-ray photos) it is possible to demonstrate or exclude heart failure in clear-cut cases. Doppler ultrasonography should be performed in all patients where heart failure is suspected but cannot be clearly demonstrated. The initial treatment for patients with heart failure with reduced systolic LV function generally consists of the administration of a thiazide or loop diuretic together with an angiotensin-converting enzyme inhibitor and a beta-blocker, to which digoxin and/or spironolactone may be added. For very old patients extra attention should be given to the comorbidity and the medication and dosing scheme should be as simple as possible. The worse the cardiac function, the more the salt and fluid intake should be limited and the more strictly the weight should be monitored.     

原发性肾病综合征并发急性肾功能衰竭17例临床与病理分析

目的观察原发性肾病综合征(iNS)并发急性肾功能衰竭(ARF)的临床和病理特征。方法对我院收治的17例iNS并发ARF患者的临床、病理特征及治疗转归进行分析,并与同期17例随机抽取的无ARF的iNS进行比较。结果iNS并发ARF多为少尿型ARF(765%):其合并高度水肿、胸腹腔积液、高血压、心衰肺水肿的比例分别为76.5%、64.7%、47.1%和58.8%,均显著高于对照组。肾小球微小病变和轻度系膜增生性肾小球肾炎占iNS并发ARF的58.8%,但两组之间肾小球病理类型的构成比无显著性差别。iNS并发ARF的小管间病变较重,均表现弥漫间质水肿,7例表现肾小管上皮细胞灶性坏死,5例伴间质炎症细胞浸润。17例iNS并发ARF患者中,2例经利尿等治疗后肾功能恢复,其余15例均行连续性肾脏替代治疗(CRRT),14例肾功能完全恢复。结论临床上iNS并发ARF多为少尿性ARF,常合并高度水肿、胸腹腔积液、高血压、心衰竭肺水肿;可发生于各种肾小球病理类型,小管间质病变均较重;经合理治疗,尤其是CRRT的应用,多预后良好。     

Withdrawing Long-Term Diuretic Treatment Among Elderly Patients in General Practice

The aim of this study was to elaborate, implement and evaluatea strategy for discontinuation of long-term diuretic treatmentin elderly patients in general practice. Thirty-three patientswere enrolled for a supervised step-down and withdrawal of diuretics.After withdrawal, the patients were followed up for 6 monthsor until diuretic treatment was re-established. Withdrawal wassuccessful according to the protocol in 18 cases. Diuretic withdrawalfailed and the treatment was re-established in 15 cases, fourof which were sudden cardiovascular events. Most withdrawalfailures were identified by routine examinations through thefollow-up programmes, thus they had few consequences for thepatients. This demonstrates that careful follow-up is essentialafter diuretic withdrawal. Our findings support the view thata large proportion of elderly patients on diuretics may notneed such treatment.     

Revival of antihypertensive therapy: use of thiazide diuretics

In the international and the Hungarian guidelines, the diuretics in the first line of the treatment of hypertension. Their sometimes false judgment is based on the side effects, because of the over dosage of the applied medication. According to finished studies, efficiency of thiazides is usually the same as that of their competitors in influencing of the cardiovascular morbidity and mortality. Thiazides have to be given in the first line an antihypertensive treatment to the patients, especially if they are old, or have a great risk for a cardiovascular complication (stroke, coronary heart disease, heart failure, left ventricular hypertrophy). In the case of natrium-retention (diabetes, obesity, nephropathy), the treatment without diuretics is not effective. Thiazides make stronger the effects especially of ACE-inhibitors, angiotensin receptor blockers, and beta receptor blockers. The newer diuretics--with fewer side effects--have very likely extrarenal way of effects, so their long time application seems very favourable.     

Diuretic use: a risk for subclinical thiamine deficiency in elderly patients

Long term diuretic therapy represents one central pharmacologic therapy of heart insufficiency and hypertension. Diuretics lead not only to an increased urinary excretion of electrolytes but also of water soluble vitamins. In this prospective study we evaluated the effect of hospitalization on the overall biochemical vitamin status in subjects older than 50 years (n=149, mean +/- SD age 70 +/- 10 years). Vitamin nutriture and other parameters were assessed at admission and discharge (duration of the hospitalization 19 +/- 1 day). Only vitamin B1 nutriture worsened during the hospitalization and in a multivariate procedure the only significant predictor of the change in the vitamin B1 nutriture was the use of diuretics during the hospitalization (F=4.06, p < 0.001). The changes in the ETK (erythrocyte transketolase activity in whole blood) and a-ETK (ETK activity coefficient) during the hospital stay correlated with the cumulative dosage of furosemide adjusted for the duration of the therapy (r = 0.36, p < 0.001 and r = - 0.28, p > 0.03). Our data suggest that hospitalized elderly are at increased risk for vitamin B1 deficiency especially when on a diuretic treatment. It is possible that a low dose thiamine supplementation my help to prevent the development of a subclinical wet-beriberi in older subjects on diuretics.     

ACE inhibitors in congestive heart failure.

Despite improved understanding of both disease mechanisms and the quality of care, congestive heart failure (CHF) remains a serious clinical problem. The traditional treatments, diuretics and digitalis, continue to play a major role in the management of many patients with CHF; however, in the last decade, angiotensin-converting enzyme (ACE) inhibitors have been added as an important treatment option. These agents counteract the overstimulation effects of diuretics on the renin-angiotensin-aldosterone system. In addition, some studies indicate that ACE inhibitors may improve symptoms and survival. Recent evidence suggests that in patients with mild to moderate CHF, ACE inhibitor and a diuretic should be administered with or without digitalis to achieve the maximum clinical benefit.     

Drug therapy for hypertension in the elderly

Essential hypertension is a major health care problem in the elderly and requires effective treatment to reduce morbidity and mortality. The traditional stepped-care approach to therapy consisted of diuretics; sympatholytic agents, or beta-blockers for all age groups. Indeed, initial therapy with these agents is effective in 50 to 60 percent of elderly patients but may produce adverse effects. A high incidence of adverse responses, including sexual dysfunction and central nervous system impairment, has been reported with diuretic or beta-blocker therapy, and a reduction in several measures of quality of life has been noted during therapy with methyldopa or propranolol. Administration of an angiotensin-converting enzyme (ACE) inhibitor is as effective as the traditional stepped-care approach without producing the ill effects associated with diuretics, sympatholytics, or beta-blockers. The combination of an ACE inhibitor with a diuretic produces additive antihypertensive effects while minimizing diuretic-induced metabolic alterations. Orthostatic hypotension with the first dose can be minimized by making sure that patients are not hypovolemic from previous diuretic therapy. Nevertheless, in controlled trials, the combination of ACE inhibitor and diuretic has been effective in up to 85 percent of patients. In addition, the use of ACE inhibitors may be beneficial in the hypertensive patient with concomitant congestive heart failure. Most important, the patient's quality of life is maintained during therapy with an ACE inhibitor alone or in combination with a diuretic. Thus, an ACE inhibitor plus a diuretic is a valuable alternative to traditional antihypertensive therapy in elderly patients.     

Pseudo-Bartter's syndrome,diuretic abuse,idiopathic edema,and eating disorders

Literature concerning Bartter's syndrome, pseudo-Bartter's syndrome, idiopathic edema, and diuretic abuse is reviewed. The authors suggest that many of the patients who present with the physiological disturbances associated with pseudo-Bartter's syndrome or with diuretic abuse, and a subgroup of those who use diuretics for idiopathic edema, have an underlying eating disorder. The pharmacology and physiology of diuretics are reviewed.     

The syndrome of hypertension and hyperkalaemia without renal failure: long term correction by thiazide diuretic

An excellent response to treatment with thiazide diuretic for twelve years is described in a patient with Gordon's Syndrome, the first to be reported from Scotland, and only the second to manifest the full clinical picture of short stature, hypertension, hyperkalaemia and hyperchloraemic acidosis without renal failure. The hypertension and biochemical abnormalities were reversed during therapy. Temporary withdrawal after seven years was followed by the immediate return of all the biochemical abnormalities, but not of the hypertension.     

Hypertension as a clinical problem: the hospital based population

A practical first step in our attack on hypertension would be the incorporation of recording blood pressure into the routine of every examination for every patient who goes to any hospital for any reason. If an elevated blood pressure is found and verified and no complications are present, antihypertensive therapy (a thiazide diuretic) should be instituted and the patient discharged to be followed as an outpatient. Patients with congestive heart failure or accelerated phase hypertension should remain in the hospital until these complications have been cleared.