A ceiling dose with furosemide in systolic heart failure: A myth or a pertinent clinical consideration?

Loop diuretics are the diuretic of choice in chronic heart failure (CHF). By prohibiting the reabsorption of sodium and chloride in the thick ascending loop of Henle, they create a hypertonic environment in the lumen, thereby keeping water from being reabsorbed in the distal convoluted tubule (DCT) or collecting duct and promoting diuresis. Loop diuretics are very effective for symptomatic relief in CHF, however there is a maximum effective dose by which higher doses will no longer improve diuresis but rather only subject the patient to side effects. Additionally, patients may also experience furosemide resistance by different mechanisms. While the true incidence of furosemide resistance is unknown, the phenomenon is a pertinent problem, which needs to be addressed to improve patient symptomatology. Focusing on the pharmacokinetic profile of furosemide, the half-life of furosemide is short. As a result, sodium retention can occur after furosemide administration, which is known as post diuretic salt retention. Furthermore, other parts of the tubule may play a role in the reabsorption and reuptake of sodium, specifically in the DCT or collecting duct, which offsets the effect of furosemide. Lastly, the concentration of furosemide at the site of action may be significantly reduced as the patient’s CHF worsens. Limiting salt intake and avoiding the use of non-steroidal anti-inflammatory drugs (NSAIDs) should always be recommended before declaring a patient to be resistant to furosemide. The clinician should consider increasing furosemide dosing frequency and/or adding another diuretic (thiazide-like); depending on the physiologic mechanism of furosemide resistance, one strategy may take preference over the other.