Clinical Pearl: Using thiazides with loop diuretics for improved diuresis in hypervolemia Benjamin Woodard, DNP, ENP-C, FNP-C, FAWM

The Problem -Here comes that readmission…that 68 year old gentleman with CHF who is back in your ED after Octoberfest, and for some reason, it is getting harder and harder to treat him! He has had a 10 kg weight gain since his last visit with his PCP, is in clear respiratory distress and has a O2sat of 85%. What now? Have you had the challenge of treating a hypervolemic CHF patient who takes heroic doses of diuretics that clearly aren’t working?

In addition to tools like BiPap, our goals in initial management often focus on the imperative of reducing intravascular and extravascular volume. However, among “loop tolerant” patients, medications like furosemide, torsemide, and bumetanide may have limited utility. Diuretic tolerance is thought to stem from rebound sodium retention, which can lead to distal nephron sodium reabsorption, and hypertrophy and hyperfunction of the distal tubule cells, resulting in in increased sodium reabsorption (Jentzer, Dewald & Hernandez, 2010).

While long-term management goals include achieving euvolemia, preventing cardiac remodeling, blood pressure control, and preservation of renal function, the emergently hypervolemic and hypoxic patient requires rapid diuresis and careful monitoring.

A Solution - One innovative way to achieve this in loop-tolerant patients is administering a thiazide, such as chlorothiazide 500 mg IV or metolazone, before administration of a loop diuretic. This closes the sodium channels in the distal convoluted tubule, which prevents reabsorption as the loop is causing inhibition of sodium and potassium reabsorption in the loop of Henle. This can result in a dramatically increased natriuresis and increase in urine output.     

Discussion - Given that the mechanism involves output of potassium and sodium, the ED clinician needs to anticipate hyponatremia and hypokalemia and should proactively consider repletion.

Likewise, given the speed of volume loss, relative hypotension should be considered and these patients should be monitored. Data on long term implications of renal function to date suggest a possible impact on short term renal function, for which hospitalized patients should be carefully monitored (Kissling & Pickworth, 2014).

References-

Jentzer, J. C., DeWald, T. A., & Hernandez, A. F. (2010). Combination of loop diuretics with thiazide-type diuretics in heart failure. Journal of the American College of Cardiology, 56(19), 1527–1534. https://doi.org/10.1016/j.jacc.2010.06.034 

Kissling, K. T., & Pickworth, K. K. (2014). Comparison of the effects of combination diuretic therapy with oral hydrochlorothiazide or intravenous chlorothiazide in patients receiving intravenous furosemide therapy for the treatment of heart failure. Pharmacotherapy, 34(8), 882–887. https://doi.org/10.1002/phar.1456 

Fliser, D., Schröter, M., Neubeck, M., & Ritz, E. (1994). Coadministration of thiazides increases the efficacy of loop diuretics even in patients with advanced renal failure. Kidney international, 46(2), 482–488. https://doi.org/10.1038/ki.1994.298

Shah, N., Madanieh, R., Alkan, M., Dogar, M. U., Kosmas, C. E., & Vittorio, T. J. (2017). A perspective on diuretic resistance in chronic congestive heart failure. Therapeutic advances in cardiovascular disease, 11(10), 271–278. https://doi.org/10.1177/1753944717718717