What is the management of volume overload with furosemide (loop diuretic) infusion in patients with heart failure with preserved ejection fraction (HFpEF)?

Furosemide Infusion in HFpEF with Volume Overload

Intravenous loop diuretics, particularly furosemide, should be administered immediately to all HFpEF patients presenting with volume overload, starting with a bolus of 20-40 mg IV (or equal to/exceeding their chronic oral daily dose if already on diuretics), with dose titration based on urine output and clinical response to achieve decongestion. 1

Initial Management Approach

Immediate Assessment and Treatment Initiation

• Begin IV loop diuretics in the emergency department or outpatient clinic without delay, as early intervention is associated with better outcomes in decompensated heart failure 1
• The initial furosemide bolus should be 20-40 mg IV for diuretic-naive patients 1, 2
• For patients already receiving oral loop diuretics, the initial IV dose must equal or exceed their chronic oral daily dose to overcome diuretic resistance 1
• Place a bladder catheter to monitor urinary output and rapidly assess treatment response 1

Dosing Strategy and Titration

The guidelines provide clear dose escalation parameters:

• Total furosemide dose should remain <100 mg in the first 6 hours and <240 mg during the first 24 hours 1, 2
• Assess urine output and signs of congestion frequently, titrating the dose accordingly 1
• When initial bolus dosing is inadequate, intensify the regimen by either: (1) higher doses of loop diuretics, (2) adding a second diuretic (metolazone, spironolactone, or IV chlorothiazide), or (3) switching to continuous infusion 1

Continuous Infusion vs. Bolus Dosing

Either continuous infusion or bolus dosing can be used, as research shows no substantial differences in outcomes between these approaches when equivalent total doses are administered. 3

• Continuous infusion may be considered after the initial starting dose in patients with evidence of volume overload 1
• A study of 41 hospitalized heart failure patients found no significant differences between bolus and continuous infusion in creatinine change (-0.02 vs 0.13 mg/dl, p=0.18), urine output (5,113 vs 4,894 ml, p=0.78), or length of stay (8.8 vs 9.9 days, p=0.69) 3
• Continuous infusion at 20 mg/hour, gradually increased up to 160 mg/hour, has proven effective in patients with diuretic resistance, achieving mean weight loss of 12.5 kg and relief of symptoms 4

HFpEF-Specific Considerations

Why Diuretics Are Essential in HFpEF

• Loop diuretics are the backbone of acute fluid overload management in HFpEF and provide symptomatic relief, though they do not improve prognosis 1
• HFpEF patients with preserved systolic function and LV hypertrophy are particularly susceptible to flash pulmonary edema due to reduced ventricular distensibility 1
• These patients frequently improve quickly with diuresis and blood pressure lowering because small changes in ventricular volume can lead to large changes in filling pressures 1
• Use the lowest effective dose in chronic management, as diuretics may stimulate the sympathetic nervous system and RAAS 1

Alternative Diuretic Considerations

• The Japanese guidelines uniquely recommend long-acting loop diuretics such as azosemide over furosemide due to comparatively reduced neurohormonal impact 1
• Torsemide (10-20 mg IV) is equivalent to furosemide 20-40 mg IV and may be preferred in some patients due to superior absorption and longer duration of action 1, 2

Managing Diuretic Resistance

Sequential Nephron Blockade

When loop diuretics alone are insufficient, add a thiazide or thiazide-like diuretic (such as metolazone) to maximize diuretic synergy through sequential nephron blockade. 1

• Thiazides (hydrochlorothiazide 25 mg PO) and aldosterone antagonists (spironolactone, eplerenone 25-50 mg PO) can be used in combination with loop diuretics 1
• Combinations in low doses are often more effective with fewer side effects than higher doses of a single drug 1
• Close monitoring of renal function and electrolytes is crucial given the increased propensity for derangement 1

Adjunctive Therapies for Refractory Cases

• Acetazolamide alongside loop diuretics has recently been shown to increase successful decongestion, though the ESC emphasizes need for further data 1
• Tolvaptan (V2 receptor antagonist) is recommended by Canadian and Japanese guidelines for fluid overload with hyponatremia or edema refractory to loop diuretics 1
• Ultrafiltration is recommended as a therapeutic "last resort" for refractory fluid overload by Japanese, NICE, and Chinese guidelines 1

Critical Monitoring Parameters

During Active Diuresis

Monitor the following daily during IV diuretic therapy: 1

• Fluid intake and output with careful measurement
• Body weight at the same time each day
• Vital signs including blood pressure (supine and standing)
• Clinical signs and symptoms of systemic perfusion and congestion
• Daily serum electrolytes (particularly potassium), urea nitrogen, and creatinine 1, 5

Electrolyte Management

The FDA label and guidelines emphasize specific electrolyte risks:

• Hypokalemia, hyponatremia, and hyperuricemia are common complications 1, 5
• Watch for signs of electrolyte imbalance: dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, or arrhythmia 5
• Digitalis therapy may exaggerate metabolic effects of hypokalemia, especially myocardial effects 5
• Abnormalities should be corrected aggressively, but diuresis should continue until fluid retention is eliminated 1

Common Pitfalls and How to Avoid Them

Underdosing Due to Fear of Complications

Excessive concern about hypotension and azotemia can lead to underutilization of diuretics and refractory edema. 1

• Persistent volume overload not only contributes to symptom persistence but may also limit efficacy and compromise safety of other HF drugs 1
• Diuresis should be maintained until fluid retention is eliminated, even if this results in mild or moderate decreases in blood pressure or renal function, as long as the patient remains asymptomatic 1

Contraindications and Cautions

• Patients with hypotension (SBP <90 mmHg), severe hyponatremia, or acidosis are unlikely to respond to diuretic treatment 1
• In patients with severe urinary retention (bladder emptying disorders, prostatic hyperplasia, urethral narrowing), furosemide can cause acute urinary retention requiring careful monitoring 5
• Patients allergic to sulfonamides may also be allergic to furosemide 5

Optimizing Response

• Inappropriately low doses of diuretics result in fluid retention, which can diminish response to ACEIs and increase risk with beta blockers 1
• Conversely, inappropriately high doses lead to volume contraction, increasing risk of hypotension with ACEIs and renal insufficiency 1
• In patients with hypoproteinemia (e.g., nephrotic syndrome), the effect of furosemide may be weakened and ototoxicity potentiated 5

Integration with Other HFpEF Therapies

SGLT2 Inhibitors as Adjunctive Therapy

Adding dapagliflozin to furosemide in type 2 diabetic patients with decompensated HFpEF showed statistically significant improvements in weight loss, diuresis parameters, and dyspnea scores without significant changes in serum potassium or kidney function. 6

• SGLT2 inhibitors are now recommended by multiple guidelines for chronic HFpEF management 1
• The combination provides enhanced diuresis without the electrolyte disturbances typical of escalating loop diuretic doses 6

Outpatient Infusion Protocols

Outpatient IV furosemide infusion protocols can prevent hospitalization in 87% of decompensating HFpEF patients, making this a viable clinical pathway for heart failure programs 7

• In a study of 105 decompensating HF patients, only 14 (13.3%) required hospital admission after outpatient IV furosemide infusion 7
• This approach requires a multidisciplinary heart failure program with clear protocols for referral to admission if no improvement occurs 7