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The Use of Diuretics in Acute Heart Failure: Evidence Based Therapy?

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The Use of Diuretics in Acute Heart Failure: Evidence Based Therapy? World Journal of Cardiovascular Diseases, 2013, 3, 25-34 WJCD http://dx.doi.org/10.4236/wjcd.2013.32A004 Published Online April 2013 (http://www.scirp.org/journal/wjcd/) The use of diuretics in acute heart failure: Evidence based therapy? Ali Vazir1*, Martin R. Cowie2 1Cardiology and Critical Care (HDU), Royal Brompton Hospital, National Heart and Lung Institute, Imperial College London, London, UK 2Cardiology, Royal Brompton Hospital, Imperial College London, London, UK Email: *[email protected], [email protected] Received 20 January 2013; revised 19 March 2013; accepted 21 April 2013 Copyright © 2013 Ali Vazir, Martin R. Cowie. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. ABSTRACT may be present where there are symptoms of poor organ perfusion as a consequence of low cardiac output and a The evidence base for the use of diuretics in acute low blood pressure. heart failure is limited, with no large double-blind Fluid retention or shift is a key feature of acute heart placebo-controlled randomized trials. However, their failure, manifesting as ankle swelling, ascites, and/or use as a first line treatment of acute heart failure is pulmonary edema. Therapeutic strategies to control fluid firmly established in clinical practice, and endorsed balance, and to shift fluid out of the interstitium, lead to in clinical guidelines. Loop diuretics are typically the significant symptomatic relief and improved health-re- first line diuretic strategy for the treatment of acute lated quality of life. heart failure. For patients with considerable fluid re- Before modern diuretics were available, the treatment tention, there is some evidence that initial treatment of fluid retention was limited to the use of such me- with continuous infusion or boluses of high dose loop chanical measures as rotating tourniquets to reduce pre- diuretic is superior to an initial lower dose strategy. load, Southey tubes inserted through the skin to drain In patients who are diuretic resistant, the addition of fluid [1] and venesection [2]. In 1785, digoxin, given in an oral thiazide or thiazide-like diuretic to induce se- the form of foxglove, was also reported to have a diuretic quential nephron blockade can be beneficial. Intra- effect, as observed by William Withering, and was the venous low-dose dopamine has also been used to as- treatment of choice for dropsy, a condition characterized sist diuresis and preserve renal function in such cir- by congestion [3]. cumstances, but trials are underway to confirm the The first diuretics that were available were mercurial clinical value of this agent. Mechanical ultrafiltration diuretics given via intramuscular injections [4]: their ef- has been used to treat patients with heart failure and fect was discovered coincidentally when patients were fluid retention, but the evidence base is not secure, treated with these drugs for syphilis. The treatment of and its place in clinical practice is yet to be estab- fluid retention in heart failure was revolutionized with lished. the development of thiazide diuretics in the 1950s [5] and loop diuretics in the 1960s [6]. Keywords: Acute Heart Failure; Diuretics; Diuretic The clinical evidence for the efficacy of diuretics in Resistance; Ultrafiltration reducing the symptoms of heart failure is based on clini- cal experience and relatively small-randomized studies. 1. INTRODUCTION Most clinical practice guidelines on the management of heart failure have given diuretic therapy a “Class I” rec- There is no universally agreed definition of acute heart ommendation (evidence and/or general agreement that a failure, but it is generally considered to represent the re- given treatment or procedure is beneficial, useful or ef- latively abrupt onset of symptoms severe enough to merit fective), with a level of evidence based on expert opinion hospitalization. It can occur de novo, or in patients with for relief of symptoms of congestion in patients present- chronic heart failure, in whom it is termed acute decom- ing with fluid retention [7,8]. pensated heart failure. In extreme cases, cardiogenic shock In the most recent European guidelines on heart failure *Corresponding author. [8] diuretics are recommended for the relief of dyspnea OPEN ACCESS 26 A. Vazir, M. R. Cowie / World Journal of Cardiovascular Diseases 3 (2013) 25-34 and edema in patients with signs and symptoms of con- dergo hepatic elimination, as opposed to furosemide which gestion, irrespective of left ventricular ejection fraction, undergoes renal elimination, therefore the latter is likely with the stated aim of achieving and maintaining eu- to accumulate with renal impairment. Absorption of oral volemia with the lowest achievable dose. It is acknowl- loop diuretics can be delayed by food. Nonsteroidal anti- edged that the dose must be adjusted, particularly after inflammatory drugs blunt the natriuretic response to all restoration of “dry body weight”, to avoid the risk of in- of the loop diuretics by preventing the prostaglandin- travascular volume depletion and dehydration, which can induced rise in renal blood flow that accompanies and lead to hypotension, renal dysfunction and the inability sustains the natriuretic response to loop diuretics. This to introduce disease modifying therapies such as angio- effect is not seen with low-dose aspirin (<1 mg/kg/day) tensin converting enzyme inhibitors, beta-blockers and [10]. mineralocorticoid receptor antagonists. All loop diuretics, but particularly furosemide, cause In this review we discuss the evidence base for the use changes in systemic hemodynamics that are initially un- of these modern diuretics in the management of acute related to the degree and extent of natriuresis that they heart failure. induce. Short-term administration of furosemide leads to a rapid increase in venous capacitance and a decline in 2. TYPES OF DIURETIC cardiac filling pressure, coincident with a rise in plasma renin activity. This effect predominates over any rise in There are four pharmacological classes of diuretics used systemic vascular resistance in patients with pulmonary in HF: edema or decompensated acute heart failure [11]. This ef- a) Loop diuretics (furosemide, bumetanide, torasemide, fect is maximized at an intravenous dose of 20 mg [12]. ethacrynic acid); All of the loop diuretics possess some ototoxicity, with b) Thiazide diuretics (hydrochlorothiazide, bendroflu- ethacrynic acid the worst. Transient hearing loss may methazide, or the “thiazide-like” metolazone); occur in patients receiving rapid intravenous bolus injec- c) Directly acting potassium-sparing diuretics (amilo- tion—so injection at a rate > 4 mg/minute is not advis- ride and triamterene); able. Permanent sensorineuronal hearing loss may occur d) Mineralocorticoid receptor antagonists (spironolo- at doses equivalent to furosemide 1000 mg per day [13]. catone, canrenoate and eplerenone). 2.2. Thiazide and Thiazide-Like Diuretics 2.1. Loop Diuretics Thiazide diuretics act on the distal tubule, where they in- Loop diuretics are the most commonly used diuretics for hibit sodium and chloride reabsorption, and block 10% - HF. They act on the ascending limb of the loop of Henle, 15% of sodium reabsorption. They cause a slower onset blocking the reabsorption of up to 20% - 30% of filtered (1 - 2 hours) and more prolonged (12 - 24 hours) but sodium by inhibiting the sodium, potassium and chloride milder diuretic effect compared to a loop diuretic. Re- co-transporter. This results in an intense, and usually bound sodium reabsorption is unlikely to occur. Despite short-lived, diuresis. The drug must be delivered to the thiazide diuretic having a less potent diuretic effect, their lumen of the nephron and is thus dependent on glomeru- long duration of action allows a similar degree of sodium lar filtration being sufficiently preserved. excretion to occur throughout a 24-hour period as com- Loop diuretics have a rapid onset of action, working pared to a loop diuretic [14]. Thiazides are more likely to within minutes when given intravenously or within 30 result in hypokalemia and nocturia as they have a longer minutes when given orally [9]. They have a short half- duration of action. Thiazides on their own are largely life, so their action is usually of short duration, and con- ineffective if glomerular filtration rate is below 30 ml/ sequently they may have to be given several times in a min, but they may be useful in combination with a loop day to maintain the diuretic effect, and to minimize re- diuretic in patients who have refractory edema. bound sodium reabsorption. They can be administered Metolazoneacts like a thiazide, but in addition it acts orally, or intravenously as a slow injection or an infusion. on the proximal tubule where 60% - 70% of sodium is All the loop diuretics are roughly equivalent in terms reabsorbed. Therefore metolozone can result in a pro- of efficacy but oral bumetanide has higher bioavailability, found diuresis when combined with a loop diuretic. It ap- pears to be effective even in moderate renal dysfunction so may be more useful than oral furosemide in patients [15]. Such combination usage is typically only required with marked fluid retention or gut absorption problems. for a few days in most cases of resistant fluid retention. Bumetanide is more potent than furosemide with a 1:40 dose equivalence. Torasemide has a longer half-life (3 - 2.3. Potassium Sparing Diuretics 4 hours), therefore can be given less frequently than fu- rosemide or bumetanide. Bumetanide and torasemide un- Potassium sparing diuretics (such as amiloride) produce Copyright © 2013 SciRes. OPEN ACCESS A. Vazir, M. R. Cowie / World Journal of Cardiovascular Diseases 3 (2013) 25-34 27 a mild diuretic effect by blocking the sodium/potassium 3. EVIDENCE BASE FOR THE USE OF exchange pump in the distal tubule. This exchanger is DIURETICSIN ACUTE HEART highly active in patients with HF who are on the combi- FAILURE nation of a loop and thiazide diuretic.
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