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Intensive Diuresis and Ultrafiltration


Common Misconceptions

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    The same diuretic doses should work for most patients regardless of renal function.

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    All patients with pulmonary edema and peripheral edema are volume overloaded.

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    Continuous infusion of loop diuretics is no more effective than intermittent bolus therapy.

    Volume overload, which is a serious complication of cardiac disease, is associated with an increased risk of respiratory failure, prolonged need for mechanical ventilation, the development of acute kidney injury, a longer stay in the hospital, and an increased mortality rate. Patients with the combination of chronic kidney disease (CKD) and heart disease are particularly at risk.

Diuretics

Types of Diuretics and Physiologic Efficacy

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    Diuretics can be classified in terms of their site of action and behavior along the nephron ( Table 18.1 ).

    Table 18.1
    Characteristics of Commonly Used Diuretics in Fluid Overload
    Type of Diuretic Site of Action Physiologic Effect Most Common Indications Related to Fluid Accumulation Most Important Side Effects
    Loop diuretics (furosemide, bumetanide) Thick ascending limb of loop of Henle Blockade of Na + /K + /Cl − cotransport system leads to inhibition of Na + reabsorption

    • AKI

    • CKD

    • CHF

    • Chronic liver disease

    • Ototoxicity

    • Hyperuricemia

    • Electrolyte disorders

    • Drug hypersensitivity

    Thiazides (bendrofluazide, hydrochlorothiazide) Metolazone Distal tubule; metolazone also acts on the loop of Henle Blockade of Na + /Cl − transport system leads to inhibition of Na + reabsorption CKD

    • Hyperglycemia

    • Drug hypersensitivity

    • Cholestatic jaundice

    • Hepatitis

    • Agranulocytosis

    Aldosterone antagonists (spironolactone) Aldosterone receptors in the distal tubule Blockade of Na + retaining action of aldosterone

    • Chronic liver disease

    • CHF

    • Gynecomastia

    • Gastrointestinal side effects

    • Drug hypersensitivity

    • Agranulocytosis

    Osmotic agents (mannitol) Active in whole nephron following glomerular filtration Reduced passive reabsorption of water Cerebral edema

    • Skin necrosis (in case of extravasation)

    • Renal failure

    • Seizures

    Potassium-sparing diuretics (amiloride, triamterene) Late portion of the distal tubule and cortical collecting duct Inhibition of K + secretion To minimize K + loss during treatment with loop diuretics or thiazides Hyperkalemia
    ANP/BNP (nesiritide) Afferent and efferent glomerular arterioles Increase in GFR by dilation of afferent glomerular arteries and constriction of efferent arteries Acute heart failure

    • Renal failure

    • Skin necrosis (in case of extravasation)

    AKI , Acute kidney injury; ANP , atrial natriuretic peptide; BNP , B-type natriuretic peptide; CHF , congestive heart failure; CKD , chronic kidney disease; GFR , glomerular filtration rate.

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    With the exception of spironolactone and mannitol, diuretics are protein bound.

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    Diuretics act from within the tubular lumen.

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    Loop diuretics are transported from the plasma into the proximal tubular cells via organic anion transporters and from there are secreted into the luminal space.

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    The quantity that enters the tubule depends on the intrinsic secretory capacity of the proximal tubule as well as the presence of other substances that also depend on cellular uptake via organic anion transporters, such as urea nitrogen and certain drugs.

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    Loop diuretics selectively block the Na + / K + /Cl 2– cotransporter in the luminal membrane of the ascending loop of Henle and generate greater water loss than sodium loss, resulting in the production of hypotonic urine.

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    Patients with an estimated glomerular filtration rate (GFR) of approximately 15 mL/min/1.73 m 2 secrete only 10% to 20% of the amount of loop diuretic secreted by patients with a normal GFR receiving the same dose.

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    Patients with a reduced GFR require higher doses to elicit a diuretic response.

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    In addition, in patients with a reduced GFR, the filtered load of extracellular fluid and sodium is lower, which limits the maximum achievable response to any further diuretic.

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    Other factors that influence drug availability in the tubular lumen and diuretic response include the actual dose administered, absolute bioavailability (for orally administered drugs), renal blood flow, and the presence of competing drugs and metabolites.

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    Diuretics have well-known side effects (see Table 18.1 ).

Indications for Intensive Diuresis

Acute Decompensated Heart Failure (ADHF)

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    Volume overload and abnormal fluid distribution are defining features of ADHF and the main reason for hospital admissions and readmissions.

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    Loop diuretics are administered in up to 90% of patients hospitalized for ADHF.

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    The margin of safety of aggressive diuresis is determined by the amount of extravascular edema and the Starling curve of the individual patient.

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    Patients with predominantly diastolic dysfunction are at greater risk of over diuresis than patients with severe systolic dysfunction.

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    The management of fluid overload in ADHF is a clinical challenge owing to the lack of consistent data from randomized controlled trials and the resulting lack of formal evidence-based treatment guidelines.

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    For decades, intravenous loop diuretics have formed the mainstay of therapy to reduce congestion and decrease ventricular filling pressures.

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    However, many patients with ADHF with preserved ejection fraction are not substantially volume overloaded despite the presence of pulmonary or peripheral edema.

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    In this case, removing too much volume may reduce the necessary preload and reduce stroke volume and cardiac output.

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    Other potential risks from administering loop diuretics in this situation include the development of neurohormonal activation, hypovolemia and systemic vasoconstriction, electrolyte disturbances, and deterioration of renal function.

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    For these reasons, aggressive diuresis should be avoided unless there is clear evidence of intravascular fluid overload.

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