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Author: Admin | 2025-04-28
For decongestion. Another metric of diuretic resistance is diuretic efficiency, which is the net fluid loss per mg of diuretic. It may be a more precise measurement of diuretic resistance then absolute diuretic dose and low diuretic efficiency has a stronger association with mortality than does absolute diuretic dose.22Although loop diuretics have not demonstrated a mortality benefit in heart failure, evidence of diuretic resistance carries a poor prognosis with a higher predicted mortality and increased risk of readmissions for heart failure.22–25 Mechanisms to explain diuretic resistance are multifactorial. In a congested state, aspects of gut wall oedema, decreased splanchnic blood flow and decreased intestinal motility due to an increased sympathetic state all lead to a delayed time to maximum peak and decreased peak concentration of the drug.10 In patients with renal insufficiency, other organic acids such as blood urea nitrogen can compete with loop diuretics for transport by the organic anion transporters, with less drug therefore reaching the site of action. This decrease in drug concentration results in a failure to reach the diuretic threshold concentration needed for the drug to be effective.Further changes in sodium handling in response to loop diuretics also contribute to diuretic resistance. During periods of decreased drug levels between diuretic doses there is a rebound in sodium reabsorption that has been termed a ‘post-diuretic effect’.26 A ‘braking phenomenon’ has also been described after chronic diuretic use due to renal adaptation. Hypertrophy of cells in the distal convoluted tubules, away from the site of action of loop diuretics, leads to increased efficiency of sodium reabsorption and decreases the effect of loop diuretics.25 And lastly, other drugs can contribute to diuretic resistance. Non-steroidal anti-inflammatory drugs are common over-the-counter medications that clinicians should ask their patients about as patients commonly view them as benign due to their availability but they can contribute to diuretic resistance as well as increased risk of hospitalisations.27Diuretic resistance and decreased response to loop diuretics is, unfortunately, not uncommon in clinical practice. Guidelines do not dictate which loop diuretic to use, only to use the lowest dose possible to achieve the desired effect.2 As
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