For a patient on high-dose furosemide without significant response, what is an appropriate strategy to improve diuresis?

When a patient on high-dose furosemide is not achieving adequate diuresis, adding a thiazide-type diuretic such as metolazone is a well-established strategy. This approach exploits a concept known as "sequential nephron blockade." Furosemide acts primarily on the ascending loop of Henle, while thiazide diuretics work on the distal convoluted tubule. By combining these two classes of diuretics, you can improve sodium and water excretion because they target different parts of the kidney's nephron and can create a synergistic effect that enhances overall diuresis.

This combination can be particularly useful in cases of refractory edema, where higher doses of a single diuretic class may not yield additional benefits. The use of metolazone or a similar thiazide-type diuretic provides an opportunity to optimize fluid removal from the body without continually escalating the dose of furosemide, which can lead to increased side effects such as electrolyte imbalances.

In contrast, increasing the dose of furosemide further may not provide an incremental benefit and could increase the risk of adverse effects. Starting a calcium channel blocker does not have a direct role in enhancing diuresis in a